Robert H Brown

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. ncbi request reprint Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing
    Niall J Lennon
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 278:50466-73. 2003
  2. ncbi request reprint Caspase-3 cleaves and inactivates the glutamate transporter EAAT2
    William Boston-Howes
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 281:14076-84. 2006
  3. ncbi request reprint A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice
    Kristin E Larsen
    Columbia University, Department of Neurology, New York, NY 10032, and Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
    Brain Res 1120:1-12. 2006
  4. doi request reprint Developmental biology. Neuron research leaps ahead
    Robert H Brown
    Massachusetts General Hospital, 16th Street, Navy Yard, Charlestown, MA 02129, USA
    Science 321:1169-70. 2008
  5. doi request reprint Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS
    Jianhong Li
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 390:947-51. 2009
  6. ncbi request reprint A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis
    Stuart L Gibb
    Farber Institute for Neurosciences, Weinberg Unit for ALS Research, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
    J Biol Chem 282:32480-90. 2007
  7. doi request reprint Recombinant GDNF: tetanus toxin fragment C fusion protein produced from insect cells
    Jianhong Li
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 385:380-4. 2009
  8. doi request reprint IGF-1:tetanus toxin fragment C fusion protein improves delivery of IGF-1 to spinal cord but fails to prolong survival of ALS mice
    Ru Ju Chian
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Building 114, 16th Street, Room 3003, Charlestown, MA 02129, USA
    Brain Res 1287:1-19. 2009
  9. doi request reprint DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS
    Wendy J Broom
    Massachusetts General Hospital, 114 16th Street, Navy Yard, Charlestown, MA 02129, USA
    Neurosci Lett 463:64-9. 2009
  10. doi request reprint 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis
    Wendy J Broom
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Amyotroph Lateral Scler 9:229-37. 2008

Detail Information

Publications76

  1. ncbi request reprint Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing
    Niall J Lennon
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 278:50466-73. 2003
    ..We propose a model of muscle membrane healing mediated by dysferlin that is relevant to both normal and dystrophic muscle and defines the annexins as potential muscular dystrophy genes...
  2. ncbi request reprint Caspase-3 cleaves and inactivates the glutamate transporter EAAT2
    William Boston-Howes
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 281:14076-84. 2006
    ..Taken together, our findings suggest that caspase-3 cleavage of EAAT2 is one mechanism responsible for the impairment of glutamate uptake in mutant SOD1-linked ALS...
  3. ncbi request reprint A glial cell line-derived neurotrophic factor (GDNF):tetanus toxin fragment C protein conjugate improves delivery of GDNF to spinal cord motor neurons in mice
    Kristin E Larsen
    Columbia University, Department of Neurology, New York, NY 10032, and Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
    Brain Res 1120:1-12. 2006
    ..These results indicate that TTC can serve as a non-viral vehicle to substantially improve the delivery of functionally active growth factors to motor neurons in the mammalian CNS...
  4. doi request reprint Developmental biology. Neuron research leaps ahead
    Robert H Brown
    Massachusetts General Hospital, 16th Street, Navy Yard, Charlestown, MA 02129, USA
    Science 321:1169-70. 2008
  5. doi request reprint Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS
    Jianhong Li
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 390:947-51. 2009
    ..These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration...
  6. ncbi request reprint A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis
    Stuart L Gibb
    Farber Institute for Neurosciences, Weinberg Unit for ALS Research, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Charlestown 02129, USA
    J Biol Chem 282:32480-90. 2007
    ....
  7. doi request reprint Recombinant GDNF: tetanus toxin fragment C fusion protein produced from insect cells
    Jianhong Li
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 385:380-4. 2009
    ..These results support further testing of recombinant GDNF:TTC as a non-viral vector to improve delivery of GDNF to brain and spinal cord in vivo...
  8. doi request reprint IGF-1:tetanus toxin fragment C fusion protein improves delivery of IGF-1 to spinal cord but fails to prolong survival of ALS mice
    Ru Ju Chian
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Building 114, 16th Street, Room 3003, Charlestown, MA 02129, USA
    Brain Res 1287:1-19. 2009
    ..IGF-1:TTC may prove to be neuroprotective in other animal models of CNS disease or injury known to be responsive to unmodified IGF-1...
  9. doi request reprint DNA sequence analysis of the conserved region around the SOD1 gene locus in recessively inherited ALS
    Wendy J Broom
    Massachusetts General Hospital, 114 16th Street, Navy Yard, Charlestown, MA 02129, USA
    Neurosci Lett 463:64-9. 2009
    ..This study disproves the hypothesis that there is a tightly linked genetic protective factor specifically located close to the SOD1 gene in SOD1(D90A) mediated ALS...
  10. doi request reprint 50bp deletion in the promoter for superoxide dismutase 1 (SOD1) reduces SOD1 expression in vitro and may correlate with increased age of onset of sporadic amyotrophic lateral sclerosis
    Wendy J Broom
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Amyotroph Lateral Scler 9:229-37. 2008
    ..Our findings suggest the hypothesis that this deletion reduces expression of the SOD1 gene and that levels of the SOD1 protein may modify the phenotype of SALS within selected populations...
  11. doi request reprint VEGF increases blood-brain barrier permeability to Evans blue dye and tetanus toxin fragment C but not adeno-associated virus in ALS mice
    Ilknur Ay
    Day Neuromuscular Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
    Brain Res 1234:198-205. 2008
    ..These data demonstrate the potential utility of VEGF for pharmacological modulation of the BBB, and indicate that the increase in BBB permeability mediated by VEGF is limited by the size of the delivered substance...
  12. doi request reprint Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats
    Charles Mills
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Eur J Neurosci 27:937-46. 2008
    ..Furthermore, although Ro5-4864 is only a very weak promoter of survival in adult neurons, it significantly enhances regeneration and functional recovery in adults...
  13. doi request reprint Dysferlin overexpression in skeletal muscle produces a progressive myopathy
    Louise E Glover
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown, MA
    Ann Neurol 67:384-93. 2010
    ..The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy...
  14. ncbi request reprint Dysferlin in membrane trafficking and patch repair
    Louise Glover
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Traffic 8:785-94. 2007
    ..This review outlines the current understanding of the role of dysferlin in membrane repair and the evolving picture of dysferlin-related signaling pathways in muscle cell physiology and pathology...
  15. ncbi request reprint Two approaches to drug discovery in SOD1-mediated ALS
    Wendy J Broom
    Day Neuromuscular Research Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Biomol Screen 11:729-35. 2006
    ..Ultimately, the authors believe that these 2 cell-based assays will provide powerful strategies to identify novel therapies for the treatment of inherited SOD1-associated forms of ALS...
  16. ncbi request reprint Variants in candidate ALS modifier genes linked to Cu/Zn superoxide dismutase do not explain divergent survival phenotypes
    Wendy J Broom
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, 114 16th Street, Navy Yard, Charlestown, 02129, USA
    Neurosci Lett 392:52-7. 2006
    ..We conclude that mutations within coding regions of genes around the SOD1 locus are not responsible for the more aggressive and more benign natures of the SOD1(A4V) and SOD1(D90A/D90A) mutations, respectively...
  17. pmc A common haplotype within the PON1 promoter region is associated with sporadic ALS
    John E Landers
    Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital East, Charlestown, MA, USA
    Amyotroph Lateral Scler 9:306-14. 2008
    ..75E-05). We conclude that a common haplotype within the PON1 promoter region is associated with susceptibility to sporadic ALS...
  18. doi request reprint Medications and laboratory parameters as prognostic factors in amyotrophic lateral sclerosis
    Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 9:369-74. 2008
    ..035). We conclude that aspirin or NSAID use may shorten survival in ALS, while calcium use may prolong survival. Our results support a need to further explore the role of neuroinflammation in the pathogenesis of ALS...
  19. doi request reprint Thrombopoietin is ineffective in a mouse model of motor neuron disease
    Andrew Caraganis
    Day Neuromuscular Laboratory, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
    Amyotroph Lateral Scler 9:354-8. 2008
    ..This treatment did not affect onset or survival in these mice. Although biologically active, demonstrated by increased platelet and TGF-beta1 levels, rmTPO did not attenuate disease progression in ALS mice...
  20. ncbi request reprint Analysis of a genetic defect in the TATA box of the SOD1 gene in a patient with familial amyotrophic lateral sclerosis
    Stephan Niemann
    Cecil B Day Laboratory for Neuromuscular Research, Harvard Medical School, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital East, Building 114, 16th Street, Charlestown, Massachusetts 02129, USA
    Muscle Nerve 36:704-7. 2007
    ..Our data suggest that this TATA box defect is not a disease-causing mutation or susceptibility factor for ALS but rather a rare polymorphism with a potential effect on SOD1 gene expression...
  21. doi request reprint Phase 2 study of sodium phenylbutyrate in ALS
    Merit E Cudkowicz
    Massachusetts General Hospital, Neurology Clinical Trials Unit, 13th Street, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 10:99-106. 2009
    ..While the majority of subjects tolerated higher dosages of NaPB, the lowest dose (9 g/day), was therapeutically efficient in improving histone acetylation levels...
  22. ncbi request reprint Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains
    Martin Ingelsson
    Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Acta Neuropathol 114:471-9. 2007
    ..In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders...
  23. ncbi request reprint Molecular biology of amyotrophic lateral sclerosis: insights from genetics
    Piera Pasinelli
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Room 3125, Building 114, 16th Street, Navy Yard, Charlestown, Massachusetts 02429, USA
    Nat Rev Neurosci 7:710-23. 2006
    ..Here, we present an overview of the mechanisms for motor neuron death and of the role of non-neuronal cells in ALS...
  24. ncbi request reprint Case records of the Massachusetts General Hospital. Case 22-2006--a 77-year-old man with a rapidly progressive gait disorder
    Gilmore N O'Neill
    Departments of Neurology, Massachusetts General Hospital, USA
    N Engl J Med 355:296-304. 2006
  25. ncbi request reprint Tetanus toxin fragment C fusion facilitates protein delivery to CNS neurons from cerebrospinal fluid in mice
    Susanna C Benn
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Neurochem 95:1118-31. 2005
    ..These results indicate that TTC may serve as a useful prototype for development as a non-viral vehicle for improving delivery of therapeutic proteins to the CNS...
  26. pmc Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis
    John E Landers
    Cecil B Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Building 114, Navy Yard, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 106:9004-9. 2009
    ..These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability...
  27. ncbi request reprint Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria
    Piera Pasinelli
    Day Laboratory for Neuromuscular Research, Department of Neurology, Harvard Medical School, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neuron 43:19-30. 2004
    ..These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein...
  28. ncbi request reprint Inhibition of SOD1 expression by mitomycin C is a non-specific consequence of cellular toxicity
    Wendy J Broom
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, MGH East, 114 16th Street, Navy Yard, Charlestown, MA 02129, USA
    Neurosci Lett 393:184-8. 2006
    ..Our data indicate the apparent inhibition of SOD1 expression by MC is a non-specific consequence of MC-induced cellular toxicity...
  29. doi request reprint Dysferlinopathies
    Anthony A Amato
    Department of Neurology, Neuromuscular Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115 6110, USA
    Handb Clin Neurol 101:111-8. 2011
    ..Muscle biopsies may be quite inflammatory, often resulting in a misdiagnosis as polymyositis. Unfortunately, there are no medical therapies available at this time...
  30. doi request reprint Overexpression of the wild-type SPT1 subunit lowers desoxysphingolipid levels and rescues the phenotype of HSAN1
    Florian S Eichler
    Massachusetts General Hospital Neuroscience Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Neurosci 29:14646-51. 2009
    ..This observation is consistent with the hypothesis that HSAN1 is the result of a gain-of-function mutation in SPTLC1 that leads to accumulation of a toxic metabolite...
  31. ncbi request reprint A survival motor neuron:tetanus toxin fragment C fusion protein for the targeted delivery of SMN protein to neurons
    Jonathan W Francis
    Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Building 114, 16th Street, Room 3003, Charlestown, MA 02129, USA
    Brain Res 995:84-96. 2004
    ..While these studies indicate that SDT may not be useful for SMA therapy, the use of the TTC:DTx fusion construct to deliver other passenger proteins to the neuronal cytosol should not be ruled out...
  32. doi request reprint Prevalence of Huntington's disease gene CAG repeat alleles in sporadic amyotrophic lateral sclerosis patients
    Eliana Marisa Ramos
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Amyotroph Lateral Scler 13:265-9. 2012
    ..These findings suggest that distinct neuronal degeneration processes are involved in these two different neurodegenerative disorders...
  33. pmc Hereditary sensory neuropathy type 1 mutations confer dominant negative effects on serine palmitoyltransferase, critical for sphingolipid synthesis
    Khemissa Bejaoui
    Day Neuromuscular Research Laboratory, Charlestown, Massachusetts, USA
    J Clin Invest 110:1301-8. 2002
    ..These results indicate that the HSN1-associated mutations in LCB1 confer dominant negative effects on the SPT enzyme...
  34. doi request reprint Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis
    Merit E Cudkowicz
    Neurology Clinical Trials Unit, Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA
    Muscle Nerve 38:837-44. 2008
    ..Arimoclomol CSF levels increased with dose. Arimoclomol was shown to be safe, and it crosses the blood-brain barrier. Serum pharmacokinetic profiles support dosing of three times per day. An efficacy study in ALS is planned...
  35. ncbi request reprint Case records of the Massachusetts General Hospital. Case 35-2006. A newborn boy with hypotonia
    Robert H Brown
    Department of Neurology, Massachusetts General Hospital, Boston, USA
    N Engl J Med 355:2132-42. 2006
  36. ncbi request reprint Human umbilical cord blood cells differentiate into muscle in sjl muscular dystrophy mice
    Kimi Y Kong
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Stem Cells 22:981-93. 2004
    ..We conclude that myogenic progenitor cells are present in the HUCB, that they can disseminate into muscle after intravenous administration, and that they are capable of myogenic differentiation in host muscle...
  37. ncbi request reprint Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy
    Alexander McCampbell
    Day Laboratory for Neuromuscular Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, 02129, USA
    Hum Mol Genet 14:3507-21. 2005
    ..These mice represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction...
  38. pmc Serum ferritin and metal levels as risk factors for amyotrophic lateral sclerosis
    Muddasir Qureshi
    Neurology Clinical Trials Unit Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA
    Open Neurol J 2:51-4. 2008
    ..We conclude that twenty-four hour urine or blood testing for metals is not warranted as part of the evaluation of ALS. Elevated levels of serum ferritin in ALS population could reflect an underlying perturbation in iron metabolism...
  39. pmc RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells
    Michele M Maxwell
    Day Laboratory for Neuromuscular Research and High Throughput Screening Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 101:3178-83. 2004
    ..The present study further supports the therapeutic potential of RNAi-based methods for the treatment of inherited human diseases, including ALS...
  40. ncbi request reprint Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes
    Peter M Andersen
    Cecil B Day Laboratory for Neuromuscular Research, Department of Neurology, Massachusetts General Hospital East and Harvard Medical School, Charlestown, MA, USA
    Amyotroph Lateral Scler Other Motor Neuron Disord 4:62-73. 2003
    ..We searched for novel SOD1 mutations and for clinical characteristics of patients with these mutations...
  41. pmc Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis
    Peter C Sapp
    Cecil B Day Laboratory for Neuromuscular Research, Massachusetts General Hospital East, Charlestown, MA 02129, USA
    Am J Hum Genet 73:397-403. 2003
    ..The analysis of these genes will delineate pathways implicated as determinants of motor-neuron viability and provide insights into possible therapies for ALS...
  42. ncbi request reprint Analysis of factors that modify susceptibility and rate of progression in amyotrophic lateral sclerosis (ALS)
    M Muddasir Qureshi
    Neurology Clinical Trials Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Amyotroph Lateral Scler 7:173-82. 2006
    ..Pertinent variables not associated with either causation or progression of ALS included physical activity, cigarette smoking and a history of physical trauma or other clinical disorders...
  43. ncbi request reprint Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency
    Mengfatt Ho
    Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Hum Mol Genet 13:1999-2010. 2004
    ..These new dysferlin-deficient mice should be useful for elucidating the pathogenic pathway in dysferlinopathy and for developing therapeutic strategies...
  44. ncbi request reprint Amyotrophic lateral sclerosis--a new role for old drugs
    Robert H Brown
    Massachusetts General Hospital, Boston, USA
    N Engl J Med 352:1376-8. 2005
  45. ncbi request reprint Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis
    Shohei Watanabe
    Department of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    Free Radic Biol Med 42:1534-42. 2007
    ..Aberrant Cu binding at the Cys111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SOD1 in models of familial ALS...
  46. pmc Small-molecule-mediated stabilization of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants against unfolding and aggregation
    Soumya S Ray
    Harvard Center for Neurodegeneration and Repair and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:3639-44. 2005
    ..In the presence of several of these molecules, A4V and other FALS-linked SOD1 mutants such as G93A and G85R behaved similarly to wild-type SOD1, suggesting that these compounds could be leads toward effective therapeutics against FALS...
  47. pmc A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q
    Collette K Hand
    Centre for Research in Neuroscience, McGill University and The Montreal General Hospital Research Institute, Montreal, Canada
    Am J Hum Genet 70:251-6. 2002
    ..The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus...
  48. ncbi request reprint Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice
    Shan Zhu
    Neuroapoptosis Laboratory, Department of Neurosurgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 24:5909-12. 2004
    ..Prophylactic creatine supplementation, similar to what is recommended for an agent such as aspirin, may be considered for patients in high stroke-risk categories...
  49. ncbi request reprint Motor unit number estimation predicts disease onset and survival in a transgenic mouse model of amyotrophic lateral sclerosis
    Jeremy M Shefner
    Department of Neurology, Upstate Medical University, Syracuse, New York 13210, USA
    Muscle Nerve 34:603-7. 2006
    ..This suggests that MUNE has potential efficacy as a useful functional outcome measure in both animal and human studies of ALS...
  50. ncbi request reprint An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis
    Soumya S Ray
    Harvard Center for Neurodegeneration and Repair and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 43:4899-905. 2004
    ..A drug-like molecule that could stabilize the A4V dimer could slow the onset and progression of FALS...
  51. ncbi request reprint Putting the heat on ALS
    Susanna C Benn
    Nat Med 10:345-7. 2004
  52. ncbi request reprint Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter
    Fernando Dangond
    Laboratory of Transcriptional and Immune Regulation, Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Physiol Genomics 16:229-39. 2004
    ..It is apparent from this study that DNA microarray analysis and appropriate bioinformatics can reveal distinct phenotypic changes that underlie the terminal stages of neurodegeneration in ALS...
  53. ncbi request reprint Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis
    Ammar Al-Chalabi
    Department of Neurology, Academic Neuroscience Centre, Institute of Psychiatry, King s College London, London, United Kingdom
    Ann Neurol 54:130-4. 2003
    ..There was no difference in age of onset, clinical presentation, rate of progression, or disease duration for those with one or two copies of the null allele, excluding CNTF as a major disease modifier in ALS...
  54. ncbi request reprint Mutant dynactin in motor neuron disease
    Imke Puls
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 33:455-6. 2003
    ..Binding assays show decreased binding of the mutant protein to microtubules. Our results show that dysfunction of dynactin-mediated transport can lead to human motor neuron disease...
  55. ncbi request reprint Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase
    Jorge A Rodriguez
    Department of Chemistry and Biochemistry, UCLA, Los Angeles, California 90095 1569, USA
    J Biol Chem 277:15932-7. 2002
    ..We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS...
  56. ncbi request reprint Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 277:15923-31. 2002
    ..Further characterization of these as-isolated SOD1 proteins may provide new insights regarding mutant SOD1 enzyme toxicity in ALS...
  57. ncbi request reprint Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice
    Hoon Ryu
    Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts, USA
    J Neurochem 93:1087-98. 2005
    ..Phenylbutyrate may therefore provide a novel therapeutic approach for the treatment of patients with ALS...
  58. ncbi request reprint Comparison of incremental with multipoint MUNE methods in transgenic ALS mice
    Jeremy M Shefner
    Department of Neurology, Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA
    Muscle Nerve 25:39-42. 2002
    ..71 for single motor unit action potential (SMUAP) amplitude and 0.95 for MUNE. In this model, therefore, both MUNE methods yield similar estimates and are equally effective at documenting progression of a lower motor neuron disorder...
  59. ncbi request reprint Age at onset in sod1-mediated amyotrophic lateral sclerosis shows familiality
    Isabella Fogh
    Neurogenetics 8:235-6. 2007
  60. ncbi request reprint A familial form of pallidoluysionigral degeneration and amyotrophic lateral sclerosis with divergent clinical presentations
    Carlos Portera-Cailliau
    UCLA Department of Neurology, Reed Neurological Research Center, 710 Westwood Plaza, Los Angeles, CA 90095, USA
    J Neuropathol Exp Neurol 66:650-9. 2007
    ..Thus, this disorder may represent a novel autosomal dominantly inherited and rapidly progressive neurodegenerative disorder with a spectrum of clinical presentations but common neuropathologic features...
  61. ncbi request reprint Mice deficient in the Rab5 guanine nucleotide exchange factor ALS2/alsin exhibit age-dependent neurological deficits and altered endosome trafficking
    Shinji Hadano
    Department of Molecular Neuroscience, The Institute of Medical Sciences, Tokai University School of Medicine, Isehara, Kanagawa 259 1193, Japan
    Hum Mol Genet 15:233-50. 2006
    ....
  62. pmc Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis
    Srikanth Ranganathan
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Neurochem 95:1461-71. 2005
    ..We validated the SELDI-TOF-MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS...
  63. pmc Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons
    Seth A Townsend
    Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Biomaterials 28:5176-84. 2007
    ..TTC-conjugated nanoparticles have the potential to serve as drug delivery vehicles targeted to the central nervous system...
  64. ncbi request reprint Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes
    Stephan Niemann
    RIKEN MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Eur J Neurosci 26:1407-20. 2007
    ..This work is the first reporting of the functional significance of NR3B in vivo and may give insight into the contribution of genetic variability of NR3B in the phenotypic heterogeneity among human population...
  65. pmc Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery
    Katrina Gwinn
    National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 2:e1254. 2007
    ..This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS...
  66. ncbi request reprint Birth order and the genetics of amyotrophic lateral sclerosis
    Umesh Vivekananda
    MRC Centre for Neurodegeneration, Research, P043, King s College London, Dept of Neurology, Institute of Psychiatry, London, SE5 8AF, UK
    J Neurol 255:99-102. 2008
    ..This is encouraging for the prospect of finding sporadic ALS susceptibility genes using genome-wide association mapping...
  67. pmc Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness
    Lawrence J Hayward
    Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Clin Invest 118:1437-49. 2008
    ....
  68. ncbi request reprint No association of DYNC1H1 with sporadic ALS in a case-control study of a northern European derived population: a tagging SNP approach
    Paresh R Shah
    Department of Neurodegenerative Disease, Institute of Neurology, London, UK
    Amyotroph Lateral Scler 7:46-56. 2006
    ....
  69. doi request reprint Evaluation of the Golgi trafficking protein VPS54 (wobbler) as a candidate for ALS
    Miriam H Meisler
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan48109 0618, USA
    Amyotroph Lateral Scler 9:141-8. 2008
    ..Several polymorphic non-synonymous SNPs were also observed in patients and controls. These initial data suggest that mutations in VPS54 are not a major cause of ALS...
  70. ncbi request reprint Heritable and pharmacological influences on pauses and apneas in inbred mice during anesthesia and emergence
    Harald Groeben
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Exp Lung Res 31:839-53. 2005
    ..This response seems to be independent from the inherited response to hypercapnia...
  71. ncbi request reprint Variants in the ALS2 gene are not associated with sporadic amyotrophic lateral sclerosis
    Ammar Al-Chalabi
    Neurogenetics 4:221-2. 2003
  72. ncbi request reprint ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis
    Matthew J Greenway
    Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
    Nat Genet 38:411-3. 2006
    ..Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration...
  73. ncbi request reprint Genetic predisposition to latex allergy: role of interleukin 13 and interleukin 18
    Robert H Brown
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Anesthesiology 102:496-502. 2005
    ..The current study tests the hypothesis that known functional polymorphisms in genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a higher frequency in healthcare workers with natural rubber latex allergy...
  74. ncbi request reprint Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis
    Yi Ju Li
    Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Neurogenetics 5:209-13. 2004
    ..Similar to our previous report, we did not find APOE associated with ALS risk. Our findings suggest that APOE may express its strongest effect through age at onset rather than on risk...
  75. ncbi request reprint The effect of leptin on the ventilatory responseto hyperoxia
    Harald Groeben
    Department of Anesthesiology and Critical Care Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
    Exp Lung Res 30:559-70. 2004
    ..Leptin deficiency abolishes the response to hyperoxia, which is restored by leptin replacement. Thus, leptin seems to be influential for a competent peripheral chemoreceptor function...
  76. ncbi request reprint Mutations in neurofilament genes are not a significant primary cause of non-SOD1-mediated amyotrophic lateral sclerosis
    Michael L Garcia
    Ludwig Institute for Cancer Research and Department of Neurosciences, University of California at San Diego, 9500 Gilman Drive, CMM E Room 3072, La Jolla, CA 92093 0670, USA
    Neurobiol Dis 21:102-9. 2006
    ..Thus, mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in ALS in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes of ALS...