muscular atrophy

Summary

Summary: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.

Top Publications

  1. ncbi Identification of ubiquitin ligases required for skeletal muscle atrophy
    S C Bodine
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591 6707, USA
    Science 294:1704-8. 2001
  2. ncbi FoxO3 controls autophagy in skeletal muscle in vivo
    Cristina Mammucari
    Venetian Institute of Molecular Medicine, 35129 Padova, Italy
    Cell Metab 6:458-71. 2007
  3. pmc Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy
    Marco Sandri
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 117:399-412. 2004
  4. ncbi FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells
    Jinghui Zhao
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 6:472-83. 2007
  5. ncbi Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
    S C Bodine
    Regeneron Pharmaceuticals, Inc 777 Old Saw Mill River Road, Tarrytown, New York 10591 6707, USA
    Nat Cell Biol 3:1014-9. 2001
  6. ncbi Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
    Stewart H Lecker
    Renal Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    FASEB J 18:39-51. 2004
  7. pmc Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
    M D Gomes
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:14440-5. 2001
  8. ncbi IKKbeta/NF-kappaB activation causes severe muscle wasting in mice
    Dongsheng Cai
    Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Cell 119:285-98. 2004
  9. ncbi Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
    C Rommel
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA
    Nat Cell Biol 3:1009-13. 2001
  10. ncbi The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors
    Trevor N Stitt
    Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA
    Mol Cell 14:395-403. 2004

Detail Information

Publications268 found, 100 shown here

  1. ncbi Identification of ubiquitin ligases required for skeletal muscle atrophy
    S C Bodine
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591 6707, USA
    Science 294:1704-8. 2001
    ..Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy...
  2. ncbi FoxO3 controls autophagy in skeletal muscle in vivo
    Cristina Mammucari
    Venetian Institute of Molecular Medicine, 35129 Padova, Italy
    Cell Metab 6:458-71. 2007
    ..These findings point to FoxO3 and Bnip3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved...
  3. pmc Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy
    Marco Sandri
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 117:399-412. 2004
    ..Thus, forkhead factor(s) play a critical role in the development of muscle atrophy, and inhibition of Foxo factors is an attractive approach to combat muscle wasting...
  4. ncbi FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells
    Jinghui Zhao
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 6:472-83. 2007
    ..These studies indicate that decreased IGF-1-PI3K-Akt signaling activates autophagy not only through mTOR but also more slowly by a transcription-dependent mechanism involving FoxO3...
  5. ncbi Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
    S C Bodine
    Regeneron Pharmaceuticals, Inc 777 Old Saw Mill River Road, Tarrytown, New York 10591 6707, USA
    Nat Cell Biol 3:1014-9. 2001
    ....
  6. ncbi Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
    Stewart H Lecker
    Renal Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    FASEB J 18:39-51. 2004
    ..Thus, different types of muscle atrophy share a common transcriptional program that is activated in many systemic diseases...
  7. pmc Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
    M D Gomes
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:14440-5. 2001
    ..Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases...
  8. ncbi IKKbeta/NF-kappaB activation causes severe muscle wasting in mice
    Dongsheng Cai
    Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA
    Cell 119:285-98. 2004
    ....
  9. ncbi Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
    C Rommel
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, USA
    Nat Cell Biol 3:1009-13. 2001
    ..In contrast, in addition to demonstrating that calcineurin does not mediate IGF-1-induced hypertrophy, we show that IGF-1 unexpectedly acts via Akt to antagonize calcineurin signalling during myotube hypertrophy...
  10. ncbi The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors
    Trevor N Stitt
    Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA
    Mol Cell 14:395-403. 2004
    ....
  11. ncbi Autophagy is required to maintain muscle mass
    Eva Masiero
    Dulbecco Telethon Institute, 35129 Padova, Italy
    Cell Metab 10:507-15. 2009
    ..Our results suggest that inhibition/alteration of autophagy can contribute to myofiber degeneration and weakness in muscle disorders characterized by accumulation of abnormal mitochondria and inclusions...
  12. pmc During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation
    Shenhav Cohen
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 185:1083-95. 2009
    ..Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1...
  13. ncbi Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival
    Xiaolan Zhou
    Departments of Metabolic Disorders and Protein Science, Amgen Research, Thousand Oaks, CA 91320, USA
    Cell 142:531-43. 2010
    ..Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival...
  14. ncbi Signaling in muscle atrophy and hypertrophy
    Marco Sandri
    Department of Biomedical Sciences, University of Padova, Padova, Italy
    Physiology (Bethesda) 23:160-70. 2008
    ..Understanding the signaling that regulates muscle mass may provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases...
  15. pmc PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription
    Marco Sandri
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:16260-5. 2006
    ..Thus, the high levels of PGC-1alpha in dark and exercising muscles can explain their resistance to atrophy, and the rapid fall in PGC-1alpha during atrophy should enhance the FoxO-dependent loss of muscle mass...
  16. pmc Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy
    Shenhav Cohen
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 198:575-89. 2012
    ..Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments...
  17. ncbi Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy
    A R La Spada
    Neurology Department, University of Pennsylvania School of Medicine, Philadelphia 19104 6146
    Nature 352:77-9. 1991
    X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity...
  18. pmc Mitochondrial fission and remodelling contributes to muscle atrophy
    Vanina Romanello
    Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padova, Italy
    EMBO J 29:1774-85. 2010
    ..In muscle this results in an orderly pattern of intermyofibrillar and subsarcolemmal mitochondria. Muscular atrophy is a genetically controlled process involving the activation of the autophagy-lysosome and the ubiquitin-..
  19. ncbi Protein degradation by the ubiquitin-proteasome pathway in normal and disease states
    Stewart H Lecker
    Nephrology Division, Beth Isreal Deaconess, Harvard Medical School, Boston, Massachusetts, USA
    J Am Soc Nephrol 17:1807-19. 2006
  20. ncbi Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling
    Xiaonan Wang
    Renal Division, WMB 338, Emory University School of Medicine, M S 1930 001 1AG, 1639 Pierce Drive, Atlanta, Georgia 30322, USA
    Endocrinology 147:4160-8. 2006
    ..Thus, insulin resistance causes muscle wasting by mechanisms that involve suppression of PI3K/Akt signaling leading to activation of caspase-3 and the ubiquitin-proteasome proteolytic pathway causing muscle protein degradation...
  21. pmc Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids
    Leslie M Baehr
    Department of Neurobiology, Physiology, and Behavior, University of California Davis, One Shields Avenue, Davis, CA 95616, USA
    J Physiol 589:4759-76. 2011
    ..These results demonstrate that MuRF1 and MAFbx do not function similarly under all atrophy models, and that the primary role of MuRF1 may extend beyond controlling protein degradation via the ubiquitin proteasome system...
  22. ncbi IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1
    Jennifer M Sacheck
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Endocrinol Metab 287:E591-601. 2004
    ..Thus an important component of growth stimulation by IGF-I, through the PI3K-Akt pathway, is its ability to rapidly suppress transcription of the atrophy-related E3 atrogin-1 and other atrogenes and degradation of myofibrillar proteins...
  23. ncbi Mechanisms of glucocorticoid-induced myopathy
    O Schakman
    Unite de Diabetologie et Nutrition, Faculte de Medecine, Universite Catholique de Louvain, 54 Avenue Hippocrate, B 1200 Brussels, Belgium
    J Endocrinol 197:1-10. 2008
    ..Promising new therapeutic approaches for treating glucocorticoid-induced muscle atrophy are also presented in this review...
  24. ncbi Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial
    Yoshihiro Sato
    Department of Neurology, Futase Social Insurance Hospital, Iizuka, Japan
    Cerebrovasc Dis 20:187-92. 2005
    ..The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-standing stroke by vitamin D supplementation...
  25. pmc The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy
    Julie Lagirand-Cantaloube
    Laboratoire de Génomique Fonctionnelle et Myogenèse, UMR866 Différenciation Cellulaire et Croissance, INRA UM II, Campus INRA SupAgro, Montpellier, France
    EMBO J 27:1266-76. 2008
    ..We conclude that eIF3-f is a key target that accounts for MAFbx function during muscle atrophy and has a major role in skeletal muscle hypertrophy. Thus, eIF3-f seems to be an attractive therapeutic target...
  26. pmc The p97/VCP ATPase is critical in muscle atrophy and the accelerated degradation of muscle proteins
    Rosanna Piccirillo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 31:3334-50. 2012
    ..Thus, p97 restrains post-natal muscle growth, and during atrophy, is essential for the accelerated degradation of most muscle proteins...
  27. ncbi Smad2 and 3 transcription factors control muscle mass in adulthood
    Roberta Sartori
    Venetian Institute of Molecular Medicine, 35129 Padova, Italy
    Am J Physiol Cell Physiol 296:C1248-57. 2009
    ..Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation, especially when they are combined with IGF-1-Akt activators...
  28. ncbi Skeletal muscle loss: cachexia, sarcopenia, and inactivity
    William J Evans
    Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC 27709, USA
    Am J Clin Nutr 91:1123S-1127S. 2010
    ..Nutritional supplementation alone may not prevent muscle loss secondary to cachexia, but, in combination with the use of an anabolic agent, it may slow or prevent muscle loss...
  29. pmc Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing
    Hugues Magne
    Clermont Universite, Universite d Auvergne, Unite de Nutrition Humaine, BP 10448, F 63000 Clermont Ferrand, France
    J Physiol 590:2035-49. 2012
    ..Thus, when supplemented with leucine-rich proteins (i.e. whey) and high protein diets, animals partially recovered the muscle mass loss...
  30. pmc Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice
    Pradyut K Paul
    Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
    J Cell Biol 191:1395-411. 2010
    ..This study unveils a novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an important therapeutic target to prevent skeletal muscle wasting...
  31. ncbi Gαi2 signaling promotes skeletal muscle hypertrophy, myoblast differentiation, and muscle regeneration
    Giulia C Minetti
    Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, 4056 Basel, Switzerland
    Sci Signal 4:ra80. 2011
    ....
  32. ncbi IL-6-induced skeletal muscle atrophy
    F Haddad
    Department of Physiology and Biophysics, University of California, Irvine, Medical Sciences 1, Irvine, CA 92697 4560, USA
    J Appl Physiol 98:911-7. 2005
    ..This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6...
  33. pmc Redox homeostasis, oxidative stress and disuse muscle atrophy
    Maria Antonietta Pellegrino
    Department of Physiology, University of Pavia, Pavia, Italy
    J Physiol 589:2147-60. 2011
    ..A precise approach to determine the levels of ROS in living cells in various conditions appears to be of paramount importance to define and support such hypotheses...
  34. ncbi Temporal alterations in protein signaling cascades during recovery from muscle atrophy
    Thomas E Childs
    Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA
    Am J Physiol Cell Physiol 285:C391-8. 2003
    ..Thus the time course of increase in molecules of signaling pathways differed as the young rat soleus muscle regrew from an atrophied state...
  35. ncbi Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease
    Mariève Doucet
    Centre de Recherche de l Hopital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l Universite Laval, Laval, Quebec, Canada
    Am J Respir Crit Care Med 176:261-9. 2007
    ..The molecular mechanisms of muscle atrophy in chronic obstructive pulmonary disease (COPD) are poorly understood. In wasted animals, muscle mass is regulated by several AKT-related signaling pathways...
  36. ncbi Skeletal muscle is a primary target of SOD1G93A-mediated toxicity
    Gabriella Dobrowolny
    Institute Pasteur Cenci Bolognetti, Department of Histology and Medical Embryology, CE BEMM and IIM, Sapienza University of Rome, Via A Scarpa, 14 Rome 00161, Italy
    Cell Metab 8:425-36. 2008
    ..These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy...
  37. ncbi TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure
    Kechun Tang
    Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0623, USA
    J Cell Physiol 222:320-7. 2010
    ....
  38. pmc Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways
    Alexander Doyle
    Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, USA
    FASEB J 25:99-110. 2011
    ..Furthermore, TLR4 knockout or p38 MAPK inhibition abolishes LPS-induced muscle proteolysis. Thus, TLR4 mediates LPS-induced muscle catabolism via coordinate activation of the ubiquitin-proteasome and the autophagy-lysosomal pathways...
  39. ncbi Signaling pathways perturbing muscle mass
    David J Glass
    Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA
    Curr Opin Clin Nutr Metab Care 13:225-9. 2010
    ..To discuss the mechanisms of muscle loss during cachexia...
  40. ncbi Accelerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus
    Lara B Pupim
    Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Kidney Int 68:2368-74. 2005
    ..Patients on renal replacement therapy (RRT) with a primary diagnosis of diabetes mellitus have the lowest survival rates along with highest hospitalization incidence...
  41. pmc The E3 ubiquitin ligase TRAF6 intercedes in starvation-induced skeletal muscle atrophy through multiple mechanisms
    Pradyut K Paul
    Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Mol Cell Biol 32:1248-59. 2012
    ..Finally, our results also identify lysine 63-linked autoubiquitination of TRAF6 as a process essential for its regulatory role in starvation-induced muscle atrophy...
  42. pmc The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle atrophy in mice
    Annabelle Z Caron
    Centre de Recherche Clinique Etienne Lebel, 3001 12th Avenue North, Sherbrooke, QC J1H5N4, Canada
    BMC Musculoskelet Disord 12:185. 2011
    ..Although several studies showed that proteasome inhibitors are efficient to reduce atrophy, no studies have demonstrated the ability of these inhibitors to preserve muscle function under catabolic condition...
  43. ncbi Inhibition of atrogin-1/MAFbx expression by adenovirus-delivered small hairpin RNAs attenuates muscle atrophy in fasting mice
    Haolong Cong
    Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People s Republic of China
    Hum Gene Ther 22:313-24. 2011
    ..Taken together, the present study showed that MAFbx could be a potential molecular target for treating muscle atrophy...
  44. ncbi Cellular markers of muscle atrophy in chronic obstructive pulmonary disease
    Pamela J Plant
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    Am J Respir Cell Mol Biol 42:461-71. 2010
    ..We conclude that muscle atrophy associated with COPD results from the recruitment of specific regulators of ubiquitin-mediated proteolytic pathways and inhibition of muscle growth...
  45. pmc Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition
    Marcus D Goncalves
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e12707. 2010
    ..Thus, we hypothesized that mice deficient in either Akt1 or Akt2 would not respond to in vivo inhibition of ActRIIB with ActRIIB-mFc treatment...
  46. ncbi Human skeletal muscle structure and function preserved by vibration muscle exercise following 55 days of bed rest
    Dieter Blottner
    Department of Vegetative Anatomy, Center of Space Medicine Berlin, Neuromuscular Group, Charite University Medicine Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195, Berlin, Germany
    Eur J Appl Physiol 97:261-71. 2006
    ..Daily short RVE should be employed as an effective atrophy countermeasure co-protocol preferentially addressing postural calf muscles during prolonged clinical immobilization or long-term human space missions...
  47. pmc NO production results in suspension-induced muscle atrophy through dislocation of neuronal NOS
    Naoki Suzuki
    Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
    J Clin Invest 117:2468-76. 2007
    ..We conclude that nNOS/NO mediates muscle atrophy via regulation of Foxo transcription factors and is a new therapeutic target for disuse-induced muscle atrophy...
  48. ncbi The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy
    Victoria C Foletta
    Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, 3125, Burwood, Australia
    Pflugers Arch 461:325-35. 2011
    ..Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function...
  49. ncbi Reduction of skeletal muscle atrophy by a proteasome inhibitor in a rat model of denervation
    Blake C Beehler
    Cardiovascular and Metabolic Diseases Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Pennington, NJ 08543, USA
    Exp Biol Med (Maywood) 231:335-41. 2006
    ..These results show that proteasome inhibition attenuates denervation-induced muscle atrophy in vivo in soleus muscles. However, this mechanism may not be operative in all types of atrophy...
  50. ncbi Molecular and phenotypic characterization of a mouse model of oculopharyngeal muscular dystrophy reveals severe muscular atrophy restricted to fast glycolytic fibres
    Capucine Trollet
    Royal Holloway, University of London, Egham, UK
    Hum Mol Genet 19:2191-207. 2010
    ..and histological analysis of the skeletal muscle of this mouse model confirmed a severe and progressive muscular atrophy associated with a reduction in muscle strength. Moreover, muscle atrophy in the A17...
  51. pmc Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy
    Isabella Palazzolo
    Neurogenetics Branch, NINDS, NIH, Bethesda, MD 20892, USA
    Neuron 63:316-28. 2009
    Expansion of a polyglutamine tract in the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA). We previously showed that Akt-mediated phosphorylation of AR reduces ligand binding and attenuates the mutant AR toxicity...
  52. ncbi Gene profiling of skeletal muscle in an amyotrophic lateral sclerosis mouse model
    Jose Luis Gonzalez de Aguilar
    Institut National de la Sante et de la Recherche Medicale, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, France
    Physiol Genomics 32:207-18. 2008
    ..Second, they identify specific gene regulations to be explored in the search for therapeutic strategies that could alleviate disease before motor neuron death manifests clinically...
  53. ncbi Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase
    Seoung Woo Lee
    Nephrology Division, Department of Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA
    J Am Soc Nephrol 15:1537-45. 2004
    ..When PI3K activity is low, both apoptotic and Ub-P'some pathways are activated coordinately to cause muscle proteolysis. This mechanism could increase muscle atrophy in conditions with impaired insulin responsiveness...
  54. pmc Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading
    Reiko Nakao
    Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto Cho, Tokushima, Japan
    Mol Cell Biol 29:4798-811. 2009
    ..The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy...
  55. pmc Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease
    Liping Zhang
    Nephrology Division, Baylor College of Medicine, Houston, Texas, USA 77030, USA
    FASEB J 25:1653-63. 2011
    ..Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics...
  56. ncbi Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases
    Igor L Baptista
    Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof Lineu Prestes, 1524, Butanta, CEP 05508 900, Sao Paulo, Brazil
    Muscle Nerve 41:800-8. 2010
    ..It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization...
  57. ncbi Muscle fiber type IIX atrophy is involved in the loss of fat-free mass in chronic obstructive pulmonary disease
    Harry R Gosker
    Department of Pulmonology, University of Maastricht, Maastricht, Netherlands
    Am J Clin Nutr 76:113-9. 2002
    ..Although the loss of peripheral muscle mass has been shown convincingly in chronic obstructive pulmonary disease (COPD), the underlying pathogenesis remains unclear...
  58. pmc TWEAK and TRAF6 regulate skeletal muscle atrophy
    Ashok Kumar
    Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202, USA
    Curr Opin Clin Nutr Metab Care 15:233-9. 2012
    ..To discuss the roles and mechanisms of action of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in skeletal muscle atrophy...
  59. ncbi Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles
    Eva Masiero
    Dulbecco Telethon Institute, Padova, Italy
    Autophagy 6:307-9. 2010
    ..In conclusion, autophagy plays a critical role for myofiber maintenance and its activation is crucial to avoid accumulation of toxic proteins and dysfunctional organelles that, in the end, would lead to atrophy and weakness...
  60. pmc IL-6 and serum amyloid A synergy mediates angiotensin II-induced muscle wasting
    Liping Zhang
    Nephrology Division, Baylor College of Medicine, Houston, TX 77030, USA
    J Am Soc Nephrol 20:604-12. 2009
    ..Targeting the high levels of IL-6 and SAA in catabolic disorders might be a therapeutic approach to prevent muscle wasting...
  61. ncbi Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress
    Douglas Paddon-Jones
    Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77550, USA
    J Clin Endocrinol Metab 91:4836-41. 2006
    ..We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength...
  62. pmc The IkappaB kinases IKKalpha and IKKbeta are necessary and sufficient for skeletal muscle atrophy
    Darin Van Gammeren
    Boston University, Boston, MA 02215, USA
    FASEB J 23:362-70. 2009
    ..These data show that both IKKalpha and IKKbeta are necessary and sufficient for physiological muscle atrophy...
  63. pmc JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy
    Anna Raffaello
    Department of Biology, Innovative Biotechnologies Interdepartmental Research Center, University of Padova, 35122 Padova, Italy
    J Cell Biol 191:101-13. 2010
    ..Therefore, JunB is important not only in dividing populations but also in adult muscle, where it is required for the maintenance of muscle size and can induce rapid hypertrophy and block atrophy...
  64. ncbi Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt
    Dawit A P Gonçalves
    Dept of Physiology, School of Medicine, Ribeirão Preto University of São Paulo, Ribeirao Preto, SP, Brazil
    Am J Physiol Endocrinol Metab 302:E123-33. 2012
    ....
  65. ncbi Posttranslational modifications control FoxO3 activity during denervation
    Enrico Bertaggia
    Venetian Institute of Molecular Medicine, Padova, Italy
    Am J Physiol Cell Physiol 302:C587-96. 2012
    ..This fine-tuning mechanism of FoxO3 regulation may be important to prevent excessive muscle loss and can be used as a therapeutic approach to counteract muscle wasting...
  66. pmc Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes
    Michael Menconi
    Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Cell Biochem 105:353-64. 2008
    ..These differences need to be taken into account when cultured myotubes are used in future studies to further explore mechanisms of muscle wasting...
  67. pmc Preferential skeletal muscle myosin loss in response to mechanical silencing in a novel rat intensive care unit model: underlying mechanisms
    Julien Ochala
    Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden
    J Physiol 589:2007-26. 2011
    ....
  68. ncbi Decrease in resting calcium and calcium entry associated with slow-to-fast transition in unloaded rat soleus muscle
    Bodvael Fraysse
    Sezione di Farmacologia, Dipartimento Farmaco Biologico, Universita degli Studi di Bari, Via Orabona 4 Campus, 70125, Bari, Italy
    FASEB J 17:1916-8. 2003
    ..According to the crucial role of resting cytosolic free calcium in the maintenance and the adaptation of muscle phenotype, our results suggest that slow-to-fast transition of HU soleus muscle is calcium dependent...
  69. ncbi The emerging roles of microRNAs in the molecular responses of metabolic rate depression
    Kyle K Biggar
    Institute of Biochemistry and Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada K1S 5B6
    J Mol Cell Biol 3:167-75. 2011
    ..Many of the same microRNAs are frequently deregulated in numerous disease pathologies and, hence, the hypometabolism model could provide a novel approach for the treatment of stroke and heart attack in humans...
  70. ncbi Work-induced changes in skeletal muscle IGF-1 and myostatin gene expression in uremia
    D F Sun
    Research Service Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
    Kidney Int 70:453-9. 2006
    ....
  71. ncbi Glycogen synthase kinase-3β is required for the induction of skeletal muscle atrophy
    Koen J P Verhees
    Department of Respiratory Medicine, School for Nutrition, Toxicology and Metabolism NUTRIM, Maastricht University Medical Centre MUMC, Maastricht, The Netherlands
    Am J Physiol Cell Physiol 301:C995-C1007. 2011
    ....
  72. ncbi Space travel directly induces skeletal muscle atrophy
    H Vandenburgh
    Department of Pathology, Brown University School of Medicine and The Miriam Hospital, Providence, Rhode Island 02906, USA
    FASEB J 13:1031-8. 1999
    ..These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development...
  73. pmc Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure
    Telma F Cunha
    School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil
    PLoS ONE 7:e41701. 2012
    ..We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF...
  74. pmc Translational suppression of atrophic regulators by microRNA-23a integrates resistance to skeletal muscle atrophy
    Shogo Wada
    Division of Regenerative Medical Engineering, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113 0033, Japan
    J Biol Chem 286:38456-65. 2011
    ..These data suggest that suppression of multiple regulators by a single miRNA can have significant consequences in adult tissues...
  75. pmc Oxidation enhances myofibrillar protein degradation via calpain and caspase-3
    Ashley J Smuder
    Center for Exercise Science, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA
    Free Radic Biol Med 49:1152-60. 2010
    ..These findings provide a mechanistic link connecting oxidative stress with accelerated myofibrillar proteolysis during disuse muscle atrophy...
  76. ncbi Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells
    Patrick O Mitchell
    Department of Pharmacology, Emory University School of Medicine, 5024 O W Rollins Research Center, Atlanta, GA 30322, USA
    Am J Physiol Cell Physiol 287:C1753-62. 2004
    ..Upon regrowth of the atrophied muscles, these deleterious effects were reversed. Our data suggest that preventing loss or dysfunction of MPC may be a new pharmacological target during muscle atrophy...
  77. ncbi Ubiquitination and proteolysis in limb and respiratory muscles of patients with chronic obstructive pulmonary disease
    Richard Debigare
    P T, Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Quebec, 2725, Chemin Ste Foy, PQ, G1V 4G5 Canada
    Proc Am Thorac Soc 7:84-90. 2010
    ..Based on this information, the reader should be able to understand the essential role of this pathway in the context of muscle homeostasis and to picture the coming research in this area...
  78. ncbi Mitochondrial biogenesis and fragmentation as regulators of muscle protein degradation
    Vanina Romanello
    Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy
    Curr Hypertens Rep 12:433-9. 2010
    ..This article reviews the rapid progress made in the past few years regarding the role of mitochondria in the control of proteolytic systems and in the loss of muscle mass and function...
  79. pmc C/EBPβ mediates tumour-induced ubiquitin ligase atrogin1/MAFbx upregulation and muscle wasting
    Guohua Zhang
    Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX 77030, USA
    EMBO J 30:4323-35. 2011
    ..Therefore, activation of the p38β MAPK-C/EBPβ signalling pathway appears a key component of the pathogenesis of LLC tumour-induced cachexia...
  80. ncbi Muscle wasting in diabetic and in tumor-bearing rats: role of oxidative stress
    Raffaella Mastrocola
    Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy
    Free Radic Biol Med 44:584-93. 2008
    ..Moreover, despite oxidative stress being detectable in both experimental models, its contribution to muscle wasting is not comparable...
  81. ncbi Prevention of muscle disuse atrophy by MG132 proteasome inhibitor
    Cecile Jamart
    Research Group in Muscle and Exercise Physiology, Institute of Neuroscience, Universite Catholique de Louvain, Place Pierre de Coubertin 1, Louvain la Neuve B 1348, Belgium
    Muscle Nerve 43:708-16. 2011
    ..Our goal was to determine whether in vivo administration of the proteasome inhibitor MG132 can prevent muscle atrophy caused by hindlimb unloading (HU)...
  82. ncbi Effects of 3 days unloading on molecular regulators of muscle size in humans
    T Gustafsson
    Department of Laboratory Medicine, Section of Clinical Physiology, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden
    J Appl Physiol (1985) 109:721-7. 2010
    ..Further, the reported difference in gene expression pattern across muscles suggests that mechanisms regulating protein content in human skeletal muscle are influenced by phenotype and/or function...
  83. pmc Absence of disturbed axonal transport in spinal and bulbar muscular atrophy
    Bilal Malik
    Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Hum Mol Genet 20:1776-86. 2011
    Spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, is a late-onset motor neuron disease (MND) caused by an abnormal expansion of the CAG repeat in the androgen receptor (AR) gene on the X-chromosome, encoding a polyglutamine ..
  84. pmc Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia
    Derek T Hall
    McGill University, Biochemistry Department, Goodman Cancer Center, Montreal, Canada
    Aging (Albany NY) 3:702-15. 2011
    ..In this review, we will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia...
  85. pmc Epo is relevant neither for microvascular formation nor for the new formation and maintenance of mice skeletal muscle fibres in both normoxia and hypoxia
    Luciana Hagström
    Laboratoire Réponses Cellulaires et Fonctionnelles à l Hypoxie, Universite Paris 13, EA 2363, 97017 Bobigny, France
    J Biomed Biotechnol 2010:137817. 2010
    ..EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency...
  86. ncbi Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction
    A M Abbatecola
    Scientific Direction, Italian National Research Center on Aging INRCA, Ancona, Italy
    J Nutr Health Aging 15:890-5. 2011
    ..We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning...
  87. ncbi Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol
    William O Kline
    Univ of California, Davis, Section of Neurobiology, Physiology, and Behavior, One Shields Ave, Davis, California 95616, USA
    J Appl Physiol 102:740-7. 2007
    ..These results demonstrate that the effects of clenbuterol are mediated, in part, through the activation of Akt and mTOR signaling pathways...
  88. pmc Decreased miR-29 suppresses myogenesis in CKD
    XIAONAN H WANG
    Renal Division, Emory University, School of Medicine, Atlanta, Georgia 30322, USA
    J Am Soc Nephrol 22:2068-76. 2011
    ..These data suggest a potential mechanism for the impaired muscle cell differentiation associated with CKD...
  89. pmc Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy
    Sarah A Reed
    Department of Physical Therapy, 101 S Newell Dr, University of Florida, Gainesville, FL 32611, USA
    FASEB J 26:987-1000. 2012
    ....
  90. ncbi Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation
    Bertrand Leger
    Clinique Romande de Réadaptation SuvaCare, Sion, Switzerland
    Rejuvenation Res 11:163-175B. 2008
    ..Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFalpha, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation...
  91. ncbi Control of muscle size during disuse, disease, and aging
    H Degens
    Institute for Biophysical and Clinical Research into Human Movement, Manchester Metropolitan University, Alsager Campus, Alsager, Cheshire, UK
    Int J Sports Med 27:94-9. 2006
    ....
  92. ncbi The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy
    A J Murton
    Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, The University of Nottingham, Queen s Medical Centre, Nottingham, UK
    Biochim Biophys Acta 1782:730-43. 2008
    ....
  93. ncbi Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model
    Mohamed Salem
    Division of Animal and Veterinary Sciences, West Virginia University, Morgantown, WV 26506 6108, USA
    Physiol Genomics 28:33-45. 2006
    ..For the first time, other changes/mechanisms unique to fish were discussed including genes associated with muscle atrophy...
  94. ncbi Comparison of CT scan muscle measurements and isokinetic trunk strength in postoperative patients
    T G Mayer
    Division of Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas
    Spine (Phila Pa 1976) 14:33-6. 1989
    ..However, no significant difference was found in strength measures between: males with high versus low pain level and working versus nonworking males at the time of evaluation...
  95. ncbi Isometric resistance exercise fails to counteract skeletal muscle atrophy processes during the initial stages of unloading
    F Haddad
    Dept of Physiology and Biophysics, Univ of California, Irvine, Irvine, CA 92697, USA
    J Appl Physiol (1985) 100:433-41. 2006
    ....
  96. ncbi The impact of sarcopenia and exercise training on skeletal muscle satellite cells
    Tim Snijders
    Department of Human Movement Sciences, Nutrition and Toxicology Research Institute Maastricht NUTRIM, Maastricht University Medical Centre, Maastricht, The Netherlands
    Ageing Res Rev 8:328-38. 2009
    ..This review discusses the contribution of skeletal muscle SC in the age-related loss of muscle mass and the efficacy of exercise training as a means to attenuate and/or reverse this process...
  97. ncbi Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1
    Bertrand Leger
    Clinique romande de réadaptation, SuvaCare, Sion, Switzerland
    FASEB J 20:583-5. 2006
    ..The transcriptional regulation of human atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR or via another signaling pathway...
  98. ncbi Cardiac defects contribute to the pathology of spinal muscular atrophy models
    Monir Shababi
    Department of Veterinary Pathobiology, Bond Life Sciences Center, School of Medicine, University of Missouri, Columbia, MO 65211, USA
    Hum Mol Genet 19:4059-71. 2010
    Spinal muscular atrophy (SMA) is an autosomal recessive disorder, which is the leading genetic cause of infantile death. SMA is the most common inherited motor neuron disease and occurs in approximately 1:6000 live births...
  99. pmc Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation
    Ryan L Mizner
    Department of Physical Therapy, 301 McKinly Laboratory, University of Delaware, Newark, Deleware 19716, USA
    J Bone Joint Surg Am 87:1047-53. 2005
    ..The purpose of the present investigation was to determine the role of failure of voluntary muscle activation and muscle atrophy in the early loss of quadriceps strength after surgery...
  100. ncbi Ubiquitin-protein ligases in muscle wasting
    Pei Rang Cao
    Renal Unit, DA517, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Int J Biochem Cell Biol 37:2088-97. 2005
    ..The emerging challenge will be to define the protein targets for, as well as to develop inhibitors of, these E3s...
  101. ncbi Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis
    Suguru Koyama
    Department of Enzymatic Regulation for Cell Functions Calpain Project, Tokyo Metropolitan Institute of Medical Science Rinshoken, Tokyo 113 8613, Japan
    J Mol Biol 376:1224-36. 2008
    ....

Research Grants73

  1. Agrin/alpha 3 Na,K-ATPase signaling at the neuromuscular junction
    Martin A Smith; Fiscal Year: 2012
    ..Disruption of this system by disease, as occurs in various myasthenic disorders, spinal muscular atrophy, and amyotrophic lateral sclerosis, toxins such as botulinum toxin, or traumatic injury, results in muscle ..
  2. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..Some of these approaches are already being tested in clinical trials for muscular dystrophy and spinal muscular atrophy, while others are still in the pre-clinical stages...
  3. Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
    Robert W Burgess; Fiscal Year: 2013
    ..CMT2D patients may present with purely motor deficits (diagnosed as distal Spinal Muscular Atrophy type V, dSMAV), whereas others carrying the same mutation present with both motor and sensory deficits...
  4. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a developmental disorder characterized by a progressive loss of motor neurons during early childhood...
  5. Innate Immune Mechanisms of Motor Neuron Injury
    Timothy Vartanian; Fiscal Year: 2010
    ..such as Primary Lateral Sclerosis, pure Hereditary Spastic Paraplegia, Kennedy's disease, Spinal Muscular Atrophy, Progressive Muscular Atrophy, and amyotrophic lateral sclerosis, as well as in viral diseases such as Polio, ..
  6. In vivo analysis of the mechanisms of axon transport.
    Catherine M Drerup; Fiscal Year: 2011
    ..in this process are associated with numerous developmental and neurodegenerative diseases such as Spinal Muscular Atrophy, Alzheimer's Disease, and Amyotrophic Lateral Sclerosis...
  7. The Role of RNA Splicing Factors in Retinal Degeneration
    Michael Farkas; Fiscal Year: 2012
    ..In this case, the neurologic disorder spinal muscular atrophy (SMA), which is caused by mutations in the survival motor neurons (SMN) gene...
  8. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is an autosomal recessive form of muscular dystrophy that afflicts approximately 1 in 6,000 live births and clinically manifests as progressive muscle weakness due to ..
  9. Noncoding RNA targets of the spinal muscular atrophy protein
    Livio Pellizzoni; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Spinal muscular atrophy (SMA) is a devastating motor neuron disease caused by decreased levels of the SMN protein...
  10. Optimization of HDAC6 Inhibitors in the Treatment of CMT
    Ludo Van Den Bosch; Fiscal Year: 2013
    ..CMT, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, is made up of a group disorders that affect peripheral nerves. CMT affects both motor and sensory nerves...
  11. SPLICING OF MRNA PRECURSORS
    Michael R Green; Fiscal Year: 2013
    ..to result in a variety of human diseases including atypical cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy and facioscapulohumeral muscular dystrophy, and has also been associated with cancer and metastasis...
  12. The survival of motor neuron protein in axonal mRNA localization
    PAUL GREGORY DONLIN-ASP; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and the second most common autosomal recessive genetic disorder worldwide...
  13. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Spinal Muscular Atrophy (SMA) is a leading genetic cause of infant mortality...
  14. A Spontaneous Mouse Model of Motor Neuron Disease
    Kevin L Seburn; Fiscal Year: 2011
    ..cause a motor neuron disease in mice that directly led to the identification of the genetic basis of Spinal Muscular Atrophy with Respiratory Distress in humans...
  15. Function of the Zinc Finger Protein ZPR1 in neurodegeneration
    LAXMAN DASS GANGWANI; Fiscal Year: 2013
    ..research is to understand the physiological role of zinc finger protein ZPR1 in the pathogenesis of spinal muscular atrophy (SMA) caused by mutation of the survival motor neurons (SMN1) gene...
  16. Cooperative lead development program for treatment of spinal muscular atrophy
    Elliot J Androphy; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Spinal Muscular Atrophy (SMA) is a common form of muscular dystrophy and the leading genetic cause of infant mortality...
  17. Role of Stasimon Dysfunction in Spinal Muscular Atrophy
    Livio Pellizzoni; Fiscal Year: 2013
    Project Summary Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy...
  18. Translating a CSF delivered AAV9-SMN for treatment of Spinal Muscular Atrophy
    Brian K Kaspar; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The autosomal recessive disorder proximal spinal muscular atrophy (SMA) is the most common genetic cause of infant death and has an incidence of 1:6,000-10,000 live births1...
  19. Improving Air Quality for Laboratory Animal Research
    Sharron S Quisenberry; Fiscal Year: 2010
    ..significant data to increase the basic understanding of diseases such as Parkinson's disease, spinal muscular atrophy, cancer, HIV-1 and food borne illnesses...
  20. Nemo-Like Kinase and the Pathogenesis of Spinal and Bulbar Muscular Atrophy
    TIFFANY WERLYNE TODD; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal and Bulbar Muscular Atrophy (SBMA, Kennedy's Disease) is an X-linked progressive neurodegenerative disease affecting the proximal spinal and bulbar motoneurons...
  21. The Role of Alternative Splicing Factor Sfrs10 in Neural Development
    Rahul N Kanadia; Fiscal Year: 2010
    ..There are several diseases such as Alzheimer's disease, myotonic dystrophy, spinal muscular atrophy and autism that are linked to defects in alternative splicing of specific genes or are caused by mutations in ..
  22. Neuronal RNA processing defects in ALS4 caused by SETX mutations
    Craig L Bennett; Fiscal Year: 2013
    ..it turns out, altered RNA processing in neurodegeneration is well established including loss of SMN in spinal muscular atrophy (SMA) and loss of FMRP in fragile-X mental retardation...
  23. Newborn screening for identification &prospective followup of infants with SMA
    Kathryn J Swoboda; Fiscal Year: 2013
    DESCRIPTION (Provided by Applicant): With an incidence of 1 in 10,000 births, spinal muscular atrophy (SMA) is one of the most common lethal genetic diseases...
  24. Mechanism Underlying Neurodegeneration Caused by Dysfunction of Pre-mRNA Splicing
    Yichang Jia; Fiscal Year: 2012
    ..The misregulation of pre-mRNA splicing has been associated with neurodegenerative disorders, including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms are largely unknown...
  25. Mechanisms of degeneration in the spinal cord and musculoskeletal system in SMA
    SANIYA FAYZULLINA; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a fatal genetic disease. It is caused by mutations in the Survival of Motor Neuron (SMN) gene and is the second most common genetic cause of childhood mortality [6]...
  26. Antisense oligonucleotides for the treatment of spinocerebellar ataxia type 2
    Daniel R Scoles; Fiscal Year: 2013
    ..and ongoing clinical trials to test ASOs for the treatment of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)...
  27. SMN Control of snRNP Biogenesis: Role in RNA Splicing and Motor Neuron Survival
    Livio Pellizzoni; Fiscal Year: 2013
    ..Reduced SMN levels cause spinal muscular atrophy (SMA)-a common inherited neuromuscular disorder characterized by motor neuron degeneration...
  28. Body Composition and Energy Utilization in Spinal Muscular Atrophy
    Douglas Michael Sproule; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a hereditary pediatric neuromuscular disease marked by progressive weakness and muscle atrophy resulting from the loss of spinal cord motor neurons...
  29. Adeno-associated Viral Vector Modification for Targeted Motor Neuron Therapy
    Nicholas M Boulis; Fiscal Year: 2010
    ..provided by applicant): Motor neuron diseases (MND), such as Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA), are progressive neurodegenerative disorders that share the common characteristic of upper and/or lower ..
  30. Defining the messenger RNP code in the brain
    EUGENE WEI MING YEO; Fiscal Year: 2013
    ..and neurological developmental defects, which can often manifest as fatal diseases such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis or life-long debilitating behavioral abnormalities such as Prader-Willi/..
  31. Regulation of SMN and Identification of its Downstream Target
    Judith Jebanathirajah Steen; Fiscal Year: 2013
    TITLE: Regulation of SMN stability and identification of its downstream targets SUMMARY Spinal Muscular Atrophy (SMA), a disease caused by the mutations of Survival Motor Neuron 1 (SMN1) gene, is the most common genetic cause of infant ..
  32. Regulatory architecture of the Androgen Receptor locus in development & evolution
    Philip L Reno; Fiscal Year: 2010
    ..of AR is associated with multiple human diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, and prostate cancer...
  33. Regulation of Sensory-Motor Connectivity by Semaphorin-Plexin Signaling
    Yutaka Yoshida; Fiscal Year: 2013
    ..cord occurs in a number of neurological disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)...
  34. Motoneuron-selective Rescue of SMA Model Mice
    Mendell Rimer; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Lower motoneuron death is believed to be the primary defect in spinal muscular atrophy (SMA), a childhood hereditary neuromuscular disease almost as prevalent as cystic fibrosis, perhaps the best-..
  35. Role of miR-8 and Ena in Synaptic Structure and Function
    CARLOS MANUEL LOYA; Fiscal Year: 2010
    ..and function has been shown to underlie neuropathologies such as Fragije X Mental Retardation, Spinal Muscular Atrophy, and autism...
  36. Motor neuron generation from SMA patient-derived induced pluripotent stem cells
    Allison D Ebert; Fiscal Year: 2010
    Spinal muscular atrophy (SMA) is the leading genetic cause of infantile death and occurs in 1:6,000 to 1:10,000 live births...
  37. A zebrafish model for neural regeneration
    ALLISON F ROSENBERG; Fiscal Year: 2012
    ..pathologies of the peripheral and central nervous systems, such as Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy. The importance of axon degeneration is highlighted by how its speed and efficiency determine the success of ..
  38. The Role of Sam68 in Synaptic Transmission and Plasticity
    Matthew Klein; Fiscal Year: 2013
    ..studies suggest that Sam68 is involved in the pathogenesis of Fragile X Tremor/Ataxia Syndrome, and Spinal Muscular Atrophy. Elucidation of Sam68's role in maintaining efficient synaptic transmission will provide valuable ..
  39. The role of Usp 14 in regulating neuronal function
    SCOTT MICHAEL WILSON; Fiscal Year: 2013
    ..in the neuromuscular junction (NMJ) have recently been reported in motor neuron diseases such as Spinal muscular atrophy (SMA);however, little is known about the pathways that regulate synaptic activity and development in motor ..
  40. TripleTOF 5600 Hybrid Mass Spectrometer
    Hanno Steen; Fiscal Year: 2012
    ..and pancreatitis, understanding the pathophysiology of Sudden Infant Death Syndrome (SIDS) and Spinal Muscular Atrophy (SMA), the identification of cytokines and receptors on sensory neurons associated with inflammatory pain and ..
  41. A Neural Development mRNA Decay Network
    Michael Cleary; Fiscal Year: 2013
    ..birth defects, including fragile X-syndrome (the most common form of hereditary mental impairment) and spinal muscular atrophy (a leading genetic cause of infant mortality)...
  42. Mechanistic Basis Underlying Protein Repair of CFTR Nonsense Mutations
    STEVEN MARK ROWE; Fiscal Year: 2010
    ..and other genetic diseases including Duchenne's muscular dystrophy, Hurler's syndrome, and spinal muscular atrophy. While initial studies with gentamicin, amikacin, and the novel small molecule PTC124 indicate significant ..
  43. Deciphering the Composition of oskar mRNP via in vivo Fluorescence Imaging
    DIANA BRATU; Fiscal Year: 2010
    ..plasticity underlying learning and memory, and may lead to diseases such as the Fragile X syndrome and spinal muscular atrophy. After nuclear transcription, mRNA is trafficked to specific destinations in the cytoplasm as mRNA: protein (..
  44. Androgen targets in a simple behavioral system
    Cynthia L Jordan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Kennedy's disease (KD, or spinal and bulbar muscular atrophy) affects men in mid-life and impairs motor function...
  45. Therapy for Spinal Muscular Atrophy
    Arthur H M Burghes; Fiscal Year: 2013
    DESCRIPTION (Provided by Applicant): Spinal muscular atrophy (SMA) is characterized by loss of motor neurons and atrophy of muscle. Proximal SMA is the second most common genetic cause of infant death...
  46. Delivery of therapeutic genes in motor neuron disease
    Don W Cleveland; Fiscal Year: 2010
    Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are fatal motor neuron disorders for which no significant treatments currently exist...
  47. New Insights into Motor Neuron Disease
    John K Fink; Fiscal Year: 2013
    ..similar approach has proven useful in studying two other motor neuron diseases, SOD1-mutation ALS and spinal muscular atrophy)...
  48. Investigation of the Establishment of the Prion State
    Irina L Derkatch; Fiscal Year: 2010
    ..Lsm4 studies may also shed light on the mechanism of spinal muscular atrophy. Strategy (B) involves designing several libraries of peptides...
  49. MODELS OF SBMA MOTOR NEURON DEGENERATION
    Albert R La Spada; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Studies of X-linked spinal &bulbar muscular atrophy (SBMA) and related motor neuron diseases have highlighted the importance of understanding the cellular and ..
  50. Mechanisms of Central Synaptic Dysfunction in SMA
    GEORGE ZACHARIAS MENTIS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy...
  51. Synapse Loss in Spinal Muscular Atrophy
    Chien Ping Ko; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Proximal Spinal Muscular Atrophy (SMA), a leading genetic cause of infant mortality, is an autosomal recessive disease characterized by the loss of spinal motoneurons, muscle atrophy, and motor ..
  52. Animal models to examine role of ZPR1 protein complexes
    LAXMAN DASS GANGWANI; Fiscal Year: 2010
    ..cause of diverse human genetic diseases ranging from cancer to neurodegenerative disorders, including spinal muscular atrophy (SMA)...
  53. A device for rapid, painless, bedside muscle evaluation of children
    JOSE LUIS BOHORQUEZ; Fiscal Year: 2012
    ..Pediatric neuromuscular disorders include muscular dystrophies, spinal muscular atrophy, and inflammatory myositis, and affect well over 100,000 children in the United States alone...
  54. Effects of early exercise on muscle and cardiovascular health after stroke
    RICHARD FRANK MACKO; Fiscal Year: 2013
    ..changes in body composition, skeletal muscle and cardiometabolic health;specific changes include paretic limb muscular atrophy, increased intramuscular fat deposition, elevated prevalence of impaired glucose tolerance and type 2 ..
  55. Characterizing an AMPA Receptor Splice Modulator in Preventing Epileptogenesis
    Melanie K Tallent; Fiscal Year: 2012
    ..antisense oligonucleotides and siRNA, and are in clinical trials for treating muscular dystrophy and spinal muscular atrophy. We have developed an SMO that specifically and potently reduces GluR1 flip in vivo...
  56. SMA mouse models: splicing manipulation and therapeutic SMN replacement
    CATHERINE DOMINGUEZ; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal Muscular Atrophy (SMA) is a neurodegenerative disease that constitutes the greatest source of genetic mortality in infants...
  57. Development of an Oral Therapeutic Drug for Spinal and Bulbar Muscular Atrophy
    Charles C Y Shih; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Spinal and bulbar muscular atrophy (SBMA or Kennedy's Disease) is a rare hereditary neurodegenerative disease that affects lower motor neurons, with progressive muscle atrophy and weakness of the ..
  58. Biogenesis of Small Ribonucleoproteins
    A Gregory Matera; Fiscal Year: 2013
    ..process is important for human health, as mutations in the SMN1 gene cause a genetic disease called Spinal Muscular Atrophy (SMA)...
  59. Comprehensive mutation detection for Neuromuscular disorders: Bringing new techno
    Madhuri R Hegde; Fiscal Year: 2010
    ..Muscular Dystrophies (LGMD), Congenital Muscular Dystrophies (CMD), Duchenne Muscular Dystrophy (DMD), Spinal Muscular Atrophy (SMA) and Charcot-Marie-Tooth disease (CMT)...
  60. Tetracycline derivatives as SMN2 mRNA splicing modifiers for treatment of SMA.
    S Ken Tanaka; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Project Summary. Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by progressive deterioration of motor neurons in the CMS. There is no treatment or cure for this disease...
  61. Metabolite Profiling of a Novel Mitochondrial Kinase in Neuromuscular Disease
    Gregory A Cox; Fiscal Year: 2013
    ..appear to progressively denervate in these mice, leading to loss of motor function resembling a distal spinal muscular atrophy. The NADKD1 protein is in the NAD Kinase family of small molecule kinases, and localizes to mitochondria, but ..
  62. Differentially Regulating Apoptosis by AR: Activating Bax or Inhibiting JNK MAPK
    Jialing Xiang; Fiscal Year: 2012
    ..This study should provide invaluable information for developing novel strategies for prevention and treatment of human diseases, such as prostate cancer and spinal and bulbar muscular atrophy.
  63. CLINICAL TRIALS FOR PEDIATRIC SPINAL MUSCULAR ATROPHY
    Susan Iannaccone; Fiscal Year: 2005
    DESCRIPTION (provided by the applicant): Spinal muscular atrophy (SMA) is a genetic disease, frequency 8 per 100,000 live births, with a high mortality during infancy and no known treatment...
  64. Genetic and Biochemical Analyses of Germline Development in Drosophila
    Alexey Arkov; Fiscal Year: 2009
    ..In particular, mutations in Tudor domain of human SMN protein cause spinal muscular atrophy which is a leading genetic cause of early childhood mortality. The following specific aims are proposed: I...
  65. GENETIC CONTROL OF NEUROMUSCULAR DEGENERATION IN MICE
    Gregory Cox; Fiscal Year: 2002
    Degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are devastating disorders that encompass both wide ranges of clinical severity and ages of onset...
  66. Large Animal Model of Spinal Muscular Atrophy
    MONIQUE LORSON; Fiscal Year: 2009
    ..by applicant): Project summary/abstract: This application proposes the generation of a swine model of Spinal Muscular Atrophy (SMA) (pSMN1-/-;hSMN2) using somatic cell nuclear transfer of gene targeted fetal fibroblasts and breeding...
  67. The Electrophysiology of Motor Neuron Diseases
    Mark Bromberg; Fiscal Year: 2002
    Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders of unknown etiology. They have in common death of lower motor neurons (LMN) causing muscle weakness, and both disorders are fatal...
  68. Novel Gene Delivery Development for Spinal Muscular Atrophy
    Brian Kaspar; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of lower motor neurons (LMNs) residing along the entire length of the spinal cord...
  69. Assembly of the AI5-beta Group I Intron RNP
    Edward Turk; Fiscal Year: 2007
    ..Defects in RNP biogenesis are responsible for retinitis pigmentosa and spinal muscular atrophy, both of which are human diseases characterized by tissue-specific degeneration of cells...
  70. microRNA biogenesis and function in spinal muscular atrophy
    Zissimos Mourelatos; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a common motor neuron disease and one of the leading genetic causes of death of young children...
  71. GOLGI APPARATUS IN AMYOTROPHIC LATERAL SCLEROSIS
    NICHOLAS GONATAS; Fiscal Year: 2001
    ..overexpressing the human heavy neurofilament subunit, and in the wobbler mouse, a model of infantile spinal muscular atrophy (reviewer 1)...
  72. The Mouse SNM Gene: Potential Role in Modeling Spinal Muscular Atrophy
    JORDAN GLADMAN; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuro-degenerative disease that is the primary genetic cause of infant mortality in the United States...
  73. Axonal Transport in a Myogenic Model of Spinal Bulbar Muscular Atrophy (SBMA)
    Michael Kemp; Fiscal Year: 2009
    ..the extent to which retrograde transport and/or endocytosis are involved in a myogenic model of Spinal Bulbar Muscular Atrophy (SBMA)...