R A Nixon

Summary

Affiliation: Nathan Kline Institute
Country: USA

Publications

  1. ncbi request reprint Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice
    Marcin Sadowski
    Department of Neurology, New York University School of Medicine, New York, New York 10016, USA
    J Neuropathol Exp Neurol 63:418-28. 2004
  2. ncbi request reprint Autophagy in neurodegenerative disease: friend, foe or turncoat?
    Ralph A Nixon
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, NY 10962, USA
    Trends Neurosci 29:528-35. 2006
  3. pmc Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease
    W Haung Yu
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    J Cell Biol 171:87-98. 2005
  4. pmc Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density
    Mala V Rao
    Center for Dementia Research, Nathan Kline Institute, NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    J Cell Biol 159:279-90. 2002
  5. pmc The myosin Va head domain binds to the neurofilament-L rod and modulates endoplasmic reticulum (ER) content and distribution within axons
    Mala V Rao
    Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York, United States of America
    PLoS ONE 6:e17087. 2011
  6. ncbi request reprint Dynamic behavior and organization of cytoskeletal proteins in neurons: reconciling old and new findings
    R A Nixon
    Nathan Kline Institute, New York University Medical Center, Orangeburg 10962, USA
    Bioessays 20:798-807. 1998
  7. ncbi request reprint Neurodegenerative lysosomal disorders: a continuum from development to late age
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York 10962, USA
    Autophagy 4:590-9. 2008
  8. pmc Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up
    Ralph A Nixon
    Department of Psychiatry, New York University School of Medicine, Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    Am J Pathol 164:757-61. 2004
  9. ncbi request reprint Autophagy, amyloidogenesis and Alzheimer disease
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    J Cell Sci 120:4081-91. 2007
  10. ncbi request reprint Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases
    Ralph A Nixon
    Department of Psychiatry, NYU School of Medicine, New York, NY 10016, USA
    Neurobiol Aging 26:373-82. 2005

Detail Information

Publications83

  1. ncbi request reprint Amyloid-beta deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice
    Marcin Sadowski
    Department of Neurology, New York University School of Medicine, New York, New York 10016, USA
    J Neuropathol Exp Neurol 63:418-28. 2004
    ..5% +/- 0.4% at 8 months to 17.4% +/- 4.6%. These findings implicate Abeta or APP in the behavioral and metabolic impairments in APP/PS1 mice and the failure to compensate functionally for PS1-related hippocampal cell loss...
  2. ncbi request reprint Autophagy in neurodegenerative disease: friend, foe or turncoat?
    Ralph A Nixon
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, NY 10962, USA
    Trends Neurosci 29:528-35. 2006
    ..In this review, we consider possible mechanisms underlying autophagy-associated cell death and their relationship to pathways mediating apoptosis and necrosis...
  3. pmc Macroautophagy--a novel Beta-amyloid peptide-generating pathway activated in Alzheimer's disease
    W Haung Yu
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    J Cell Biol 171:87-98. 2005
    ..Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD...
  4. pmc Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density
    Mala V Rao
    Center for Dementia Research, Nathan Kline Institute, NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    J Cell Biol 159:279-90. 2002
    ....
  5. pmc The myosin Va head domain binds to the neurofilament-L rod and modulates endoplasmic reticulum (ER) content and distribution within axons
    Mala V Rao
    Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York, United States of America
    PLoS ONE 6:e17087. 2011
    ..Based on observations that the Myo Va motor domain binds to intermediate filament (IF) proteins of several classes, Myo Va interactions with IFs may serve similar roles in organizing organelle topography in different cell types...
  6. ncbi request reprint Dynamic behavior and organization of cytoskeletal proteins in neurons: reconciling old and new findings
    R A Nixon
    Nathan Kline Institute, New York University Medical Center, Orangeburg 10962, USA
    Bioessays 20:798-807. 1998
    ..This regulation involves, in part, a system of protein kinases and phosphatases modulated by both intercellular and intracellular signals. Conceptual models of slow axonal transport have evolved to accommodate these new findings...
  7. ncbi request reprint Neurodegenerative lysosomal disorders: a continuum from development to late age
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York 10962, USA
    Autophagy 4:590-9. 2008
    ..We highlight Alzheimer's disease as a disease within this group and discuss how each of the genes and other risk factors promoting this disease contribute to progressive lysosomal dysfunction and neuronal cell death...
  8. pmc Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up
    Ralph A Nixon
    Department of Psychiatry, New York University School of Medicine, Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    Am J Pathol 164:757-61. 2004
    ..In this commentary, the common features of endosome dysfunction are reviewed. Emerging evidence that endosome dysfunction may lead to beta-amyloidogenic APP processing or neurodegeneration by several different means is discussed...
  9. ncbi request reprint Autophagy, amyloidogenesis and Alzheimer disease
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    J Cell Sci 120:4081-91. 2007
    ..The combination of increased autophagy induction and defective clearance of Abeta-generating autophagic vacuoles creates conditions favorable for Abeta accumulation in Alzheimer disease...
  10. ncbi request reprint Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases
    Ralph A Nixon
    Department of Psychiatry, NYU School of Medicine, New York, NY 10016, USA
    Neurobiol Aging 26:373-82. 2005
    ....
  11. ncbi request reprint Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, New York 10962, USA
    J Neuropathol Exp Neurol 64:113-22. 2005
    ..The striking accumulations of immature AV forms in dystrophic neurites suggest that the transport of AVs and their maturation to lysosomes may be impaired, thereby impeding the suspected neuroprotective functions of autophagy...
  12. ncbi request reprint The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review
    R A Nixon
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    Neurochem Res 25:1161-72. 2000
    ..These and other studies support the view that the progressive alterations of lysosomal function observed during aging and Alzheimer's disease contribute importantly to the neurodegenerative process in Alzheimer's disease...
  13. pmc Autophagy failure in Alzheimer's disease--locating the primary defect
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Neurobiol Dis 43:38-45. 2011
    ..This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."..
  14. ncbi request reprint A "protease activation cascade" in the pathogenesis of Alzheimer's disease
    R A Nixon
    Center for Dementia Research, Nathan Kline Institute, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA
    Ann N Y Acad Sci 924:117-31. 2000
    ....
  15. ncbi request reprint Lysosomal system pathways: genes to neurodegeneration in Alzheimer's disease
    Ralph A Nixon
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    J Alzheimers Dis 9:277-89. 2006
    ....
  16. ncbi request reprint The calpains in aging and aging-related diseases
    Ralph A Nixon
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    Ageing Res Rev 2:407-18. 2003
    ..The early and pervasive involvement of calpains in Alzheimer's disease potentially influences the development of beta-amyloid and tau disturbances and their consequences for neurodegeneration and neuronal cell loss...
  17. pmc Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations
    A M Cataldo
    Nathan S Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA
    Am J Pathol 157:277-86. 2000
    ....
  18. ncbi request reprint Deleting the phosphorylated tail domain of the neurofilament heavy subunit does not alter neurofilament transport rate in vivo
    Aidong Yuan
    Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Neurosci Lett 393:264-8. 2006
    ..Possible roles for tail domains as cross-bridges between a neurofilament and its neighbors or other cytoskeletal elements is discussed...
  19. ncbi request reprint Alzheimer's disease-related overexpression of the cation-dependent mannose 6-phosphate receptor increases Abeta secretion: role for altered lysosomal hydrolase distribution in beta-amyloidogenesis
    Paul M Mathews
    Nathan Kline Institute and New York University School of Medicine, Orangeburg, New York 10962, USA
    J Biol Chem 277:5299-307. 2002
    ....
  20. pmc Anesthesia-induced hyperphosphorylation detaches 3-repeat tau from microtubules without affecting their stability in vivo
    Emmanuel Planel
    Taub Institute for Alzheimer s Disease Research, Department of Pathology, Columbia University Medical Center, New York, New York 10032, USA
    J Neurosci 28:12798-807. 2008
    ..Tau remaining on the MTs under these conditions is sufficient to maintain MT network integrity...
  21. pmc Marked calpastatin (CAST) depletion in Alzheimer's disease accelerates cytoskeleton disruption and neurodegeneration: neuroprotection by CAST overexpression
    Mala V Rao
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 28:12241-54. 2008
    ..CAST mimetics may, therefore, be neuroprotective in AD...
  22. pmc Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease
    - Veeranna
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA
    Am J Pathol 165:795-805. 2004
    ....
  23. ncbi request reprint Rab5-stimulated up-regulation of the endocytic pathway increases intracellular beta-cleaved amyloid precursor protein carboxyl-terminal fragment levels and Abeta production
    Olivera M Grbovic
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 278:31261-8. 2003
    ..Our findings in this model system suggest that the endosomal pathology seen at the earliest stage of sporadic AD may contribute to APP proteolysis along a beta-amyloidogenic pathway...
  24. ncbi request reprint Calpain inhibitors, a treatment for Alzheimer's disease: position paper
    Fortunato Battaglia
    Department of Psychiatry, Nathan Kline Institute for Psychiatric Research, NYU School of Medicine, Orangeburg, NY 10962, USA
    J Mol Neurosci 20:357-62. 2003
    ..Findings derived from these studies will provide a novel approach to cognitive enhancement in Alzheimer's disease...
  25. ncbi request reprint Overexpression of human cystatin C in transgenic mice does not affect levels of endogenous brain amyloid Beta Peptide
    Monika Pawlik
    Department of Pharmacology, New York University School of Medicine, New York, NY, 10016, USA
    J Mol Neurosci 22:13-8. 2004
    ..Thus, in vivo overexpression of human cystatin C does not affect Abeta levels in mice that do not deposit Abeta...
  26. pmc Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases
    - Veeranna
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA
    J Neurochem 107:35-49. 2008
    ..The regulation of a single target by multiple protein kinases underscores the importance of monitoring other relevant kinases when the activity of a particular one is blocked...
  27. ncbi request reprint Aging, gender and APOE isotype modulate metabolism of Alzheimer's Abeta peptides and F-isoprostanes in the absence of detectable amyloid deposits
    Jun Yao
    Department of Psychiatry, New York University, The Nathan S Kline Institute for Psychiatric Research, Orangeburg, New York, USA
    J Neurochem 90:1011-8. 2004
    ....
  28. pmc Alzheimer's-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition
    Ying Jiang
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    Proc Natl Acad Sci U S A 107:1630-5. 2010
    ....
  29. ncbi request reprint Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation
    Magdalena Sastre
    Departments of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA
    Neurobiol Aging 25:1033-43. 2004
    ..Notably, cystatin C association with Abeta results in a concentration-dependent inhibition of Abeta fibril formation...
  30. ncbi request reprint Autophagic vacuoles are enriched in amyloid precursor protein-secretase activities: implications for beta-amyloid peptide over-production and localization in Alzheimer's disease
    W H Yu
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Int J Biochem Cell Biol 36:2531-40. 2004
    ....
  31. pmc Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations
    Ju Hyun Lee
    Center for Dementia Research, Nathan S Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Cell 141:1146-58. 2010
    ..Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets...
  32. ncbi request reprint Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration
    Balapal S Basavarajappa
    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA
    Mini Rev Med Chem 9:448-62. 2009
    ..In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed...
  33. pmc Regional selectivity of rab5 and rab7 protein upregulation in mild cognitive impairment and Alzheimer's disease
    Stephen D Ginsberg
    Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, Orangeburg, NY 10962, USA
    J Alzheimers Dis 22:631-9. 2010
    ....
  34. pmc Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer's disease progression
    Stephen D Ginsberg
    Center for Dementia Research, Nathan Kline Institute, New York University Langone Medical Center, Orangeburg, NY 10962, USA
    Biol Psychiatry 68:885-93. 2010
    ....
  35. pmc Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease
    Fabrizio Trinchese
    Department of Pathology and Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University, New York, New York, USA
    J Clin Invest 118:2796-807. 2008
    ..Thus, calpain inhibition may prove useful in the alleviation of memory loss in AD...
  36. pmc Neuronal apoptosis and autophagy cross talk in aging PS/APP mice, a model of Alzheimer's disease
    Dun Sheng Yang
    Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, 140 Old Orangeburg Rd, Bldg 39, Orangeburg, NY 10962, USA
    Am J Pathol 173:665-81. 2008
    ..Our findings establish apoptosis as a mode of neuronal cell death in aging PS/APP mice and identify the cross talk between autophagy and apoptosis, which influences neuronal survival in AD-related neurodegeneration...
  37. ncbi request reprint Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS
    Aidong Yuan
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 26:10006-19. 2006
    ....
  38. ncbi request reprint Cortical plasticity in Alzheimer's disease in humans and rodents
    Fortunato Battaglia
    City University of New York CUNY School of Medicine, Nathan Kline Institute, Orangeburg, New York, USA
    Biol Psychiatry 62:1405-12. 2007
    ..We then ascertained whether this deficit might be paralleled by functional abnormalities of N-methyl-D-aspartate (NMDAR) glutamate receptors...
  39. pmc Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice
    Aidong Yuan
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 28:1682-7. 2008
    ..These results suggest that tau is not essential for axonal transport and that transport rates in vivo are not significantly affected by substantial fluctuations in tau expression...
  40. pmc Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model
    Daniel W Wesson
    Emotional Brain Institute and Center for Dementia Research, Nathan S Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA
    J Neurosci 30:505-14. 2010
    ..Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta...
  41. pmc Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model
    Jennifer H K Choi
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurochem 110:1818-27. 2009
    ..Therefore, multiple mechanisms contribute to the regulation towards diploid levels of APP metabolites in the Ts65Dn mouse brain...
  42. pmc Neurofilaments form a highly stable stationary cytoskeleton after reaching a critical level in axons
    Aidong Yuan
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 29:11316-29. 2009
    ..These findings reconcile in vitro and in vivo axonal transport observations, showing that slowly transported NFs or subunit oligomers are precursors to a highly stable stationary cytoskeletal network that supports mature axons...
  43. ncbi request reprint Calpain activity regulates the cell surface distribution of amyloid precursor protein. Inhibition of calpains enhances endosomal generation of beta-cleaved C-terminal APP fragments
    Paul M Mathews
    Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Biol Chem 277:36415-24. 2002
    ....
  44. ncbi request reprint MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease
    Joseph A Helpern
    Nathan S Kline Institute, Orangeburg, New York 10962, USA
    Magn Reson Med 51:794-8. 2004
    ..No differences in T(1) values or proton density were detected between any groups of mice. These results indicate that T(2) may be a sensitive marker of abnormalities in this transgenic mouse model of AD...
  45. ncbi request reprint Neurofilament transport in vivo minimally requires hetero-oligomer formation
    Aidong Yuan
    Center for Dementia Research, Nathan Kline Institute, New York University School of Medicine, Orangeburg, New York 10962, USA
    J Neurosci 23:9452-8. 2003
    ..They also show that NF-M can partner with intermediate filament proteins other than the NF-H and NF-L subunits in neurons to support slow transport and possibly other functions of neuronal intermediate filaments...
  46. ncbi request reprint Defective neurofilament transport in mouse models of amyotrophic lateral sclerosis: a review
    Mala V Rao
    Center for Dementia Research, Nathan Kline Institute Department of Psychiatry, NYU School of Medicine, 140 Old Orangeburg Road, Orangeburg, New York 10962, USA
    Neurochem Res 28:1041-7. 2003
    ..This review addresses axonal transport in mouse models of ALS and the special significance of neurofilament transport in this disease...
  47. ncbi request reprint Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice
    Maria F Falangola
    Center for Advanced Brain Imaging, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Neurochem Res 30:201-5. 2005
    ....
  48. pmc The neurofilament middle molecular mass subunit carboxyl-terminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate
    Mala V Rao
    Nathan Kline Institute, NYU School of Medicine, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA
    J Cell Biol 163:1021-31. 2003
    ....
  49. ncbi request reprint Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents
    Sang Pil Lee
    Center for Advanced Brain Imaging, The Nathan Kline Institute, Orangeburg, NY 10962, USA
    Magn Reson Med 52:538-44. 2004
    ..Furthermore, the detection of beta-amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging...
  50. ncbi request reprint Calpain inhibitors: a treatment for Alzheimer's disease
    Gabriella Di Rosa
    Nathan Kline Institute, NYU School of Medicine, Orangeburg, NY 10962, USA
    J Mol Neurosci 19:135-41. 2002
    ..Therefore, we will also test whether we can rescue the learning impairment through a treatment with calpain inhibitors...
  51. pmc Gene replacement in mice reveals that the heavily phosphorylated tail of neurofilament heavy subunit does not affect axonal caliber or the transit of cargoes in slow axonal transport
    Mala V Rao
    Nathan Kline Institute, New York University School of Medicine, Orangeburg, NY 10962, USA
    J Cell Biol 158:681-93. 2002
    ..Most surprisingly, at least in optic nerve axons, loss of the NF-H tail does not affect the rate of transport of neurofilament subunits...
  52. pmc Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease
    P M Mathews
    Nathan Kline Institute, New York University School of Medicine, Organgeburg, New York 10962, USA
    Mol Med 6:878-91. 2000
    ..Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD)...
  53. ncbi request reprint P301L tauopathy: confocal immunofluorescence study of perinuclear aggregation of the mutated protein
    Emil Adamec
    Department of Psychiatry, Harvard Medical School, Mailman Research Center, Laboratories for Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
    J Neurol Sci 200:85-93. 2002
    ..Absence of immunostaining for ubiquitin indicates possible dysfunction of the ubiquitin-proteasome system in this tauopathy...
  54. doi request reprint Monitoring autophagy in Alzheimer's disease and related neurodegenerative diseases
    Dun Sheng Yang
    Center for Dementia Research, Nathan S Kline Institute, Orangeburg, New York, USA
    Methods Enzymol 453:111-44. 2009
    ....
  55. pmc The contributions of myelin and axonal caliber to transverse relaxation time in shiverer and neurofilament-deficient mouse models
    Victor V Dyakin
    Center for Dementia Research, Nathan Kline Institute Orangeburg, New York 10962, USA
    Neuroimage 51:1098-105. 2010
    ..Our findings indicate that T2 is strongly influenced by myelination state and axonal volume, while neurofilament structure within the intra-axonal compartment has a lesser effect upon single compartment T2 estimates...
  56. ncbi request reprint Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models
    Weiqian Mi
    Nathan S Kline Institute, Orangeburg, New York 10962, USA
    Nat Genet 39:1440-2. 2007
    ..Thus, cystatin C has a protective role in Alzheimer's disease pathogenesis, and modulation of cystatin C concentrations may have therapeutic implications for the disease...
  57. ncbi request reprint Calpain activation in neurodegenerative diseases: confocal immunofluorescence study with antibodies specifically recognizing the active form of calpain 2
    Emil Adamec
    Department of Psychiatry, Harvard Medical School, Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
    Acta Neuropathol 104:92-104. 2002
    ..Overall, these results provide evidence of the important role of the calpain proteolytic system in the pathogenesis of neurodegenerative diseases with tau neurofibrillary pathology...
  58. ncbi request reprint Tissue processing prior to protein analysis and amyloid-beta quantitation
    Stephen D Schmidt
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA
    Methods Mol Biol 299:267-78. 2005
    ..The ELISA technique is described in detail in the following chapter...
  59. pmc In vivo MRI identifies cholinergic circuitry deficits in a Down syndrome model
    Yuanxin Chen
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, United States
    Neurobiol Aging 30:1453-65. 2009
    ..These results establish the utility of quantitative MRI in vivo for identifying Alzheimer's disease-relevant cholinergic changes in animal models of DS and characterizing the selective vulnerability of cholinergic neuron subpopulations...
  60. pmc Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing
    Hirokazu Okada
    Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University Medical Center, New York, New York, USA
    FASEB J 24:2783-94. 2010
    ..Our study identifies a novel cellular pathway by which SNX6 negatively modulates BACE1-mediated cleavage of APP...
  61. pmc Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease
    Barry Boland
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA
    J Neurosci 28:6926-37. 2008
    ..Therapeutic modulation of autophagy in AD may, therefore, require targeting late steps in the autophagic pathway...
  62. ncbi request reprint ELISA method for measurement of amyloid-beta levels
    Stephen D Schmidt
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA
    Methods Mol Biol 299:279-97. 2005
    ..Here we describe methods for the recovery of both soluble and deposited Abeta from brain tissue and the subsequent quantitation of the peptide by sandwich ELISA...
  63. pmc Complexes of amyloid-beta and cystatin C in the human central nervous system
    Weiqian Mi
    Nathan S Kline Institute, Orangeburg, New York, USA
    J Alzheimers Dis 18:273-80. 2009
    ..Thus, enhancing CysC expression or modulating CysC binding to Abeta have important disease-modifying effects, suggesting a novel therapeutic intervention for AD...
  64. pmc Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits
    Dun Sheng Yang
    Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962, USA
    Brain 134:258-77. 2011
    ..Our findings support the pathogenic significance of autophagic-lysosomal dysfunction in Alzheimer's disease and indicate the potential value of restoring normal autophagy as an innovative therapeutic strategy for Alzheimer's disease...
  65. ncbi request reprint Alzheimer amyloid precursor aspartyl proteinase activity in CHAPSO homogenates of Spodoptera frugiperda cells
    Troy L Carter
    Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Alzheimer Dis Assoc Disord 18:261-3. 2004
    ..Immunoprecipitation-mass spectrometry of AICD-L revealed its identity as the minor of the two known AICDs...
  66. ncbi request reprint Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases
    David Butler
    Department of Pharmaceutical Sciences and the Neurosciences Program, University of Connecticut, Storrs, Connecticut 06269 3092, USA
    Autophagy 2:234-7. 2006
    ..Positive modulation of protein degradation processes represents a strategy to promote clearance of toxic accumulations and to slow the synaptopathogenesis and associated cognitive decline in aging-related dementias...
  67. ncbi request reprint Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration
    Ahmad Salehi
    Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA
    Neuron 51:29-42. 2006
    ..Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration...
  68. pmc Down syndrome fibroblast model of Alzheimer-related endosome pathology: accelerated endocytosis promotes late endocytic defects
    Anne M Cataldo
    Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
    Am J Pathol 173:370-84. 2008
    ....
  69. ncbi request reprint Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and Down syndrome
    Anne M Cataldo
    Mailman Research Center, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
    Neurobiol Aging 25:1263-72. 2004
    ....
  70. pmc Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases
    Peter Mastrangelo
    Centre for Research in Neurodegenerative Diseases, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 3H2
    Proc Natl Acad Sci U S A 102:8972-7. 2005
    ..Instead, our studies define functionally distinct gamma-secretase variants. We speculate that extrinsic components, in combination with core complexes, may tailor functional variants of this enzyme to their preferred substrates...
  71. ncbi request reprint Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins
    Dun Sheng Yang
    Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 277:28135-42. 2002
    ....
  72. ncbi request reprint Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases
    Aubrey D N J de Grey
    Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK
    Ageing Res Rev 4:315-38. 2005
    ..We discuss how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose and ways to avoid potential side-effects...
  73. ncbi request reprint Characterization of erasin (UBXD2): a new ER protein that promotes ER-associated protein degradation
    Jing Liang
    Graduate Program in Molecular Medicine, and Institute for Neurodegenerative Diseases, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA
    J Cell Sci 119:4011-24. 2006
    ..These results suggest that erasin may be involved in ERAD and in Alzheimer's disease...
  74. ncbi request reprint Presenilin mutations in familial Alzheimer disease and transgenic mouse models accelerate neuronal lysosomal pathology
    Anne M Cataldo
    Laboratory for Molecular Neuropathology, Mailman Research Center, McLean Hospital, Belmont, Massachusetts, USA
    J Neuropathol Exp Neurol 63:821-30. 2004
    ..Our findings suggest that presenilin mutations have amyloid-independent effects on the lysosomal system, which are synergistic with the lysosomal system pathology that is associated with beta-amyloid...
  75. ncbi request reprint Co-expressed presenilin 1 NTF and CTF form functional gamma-secretase complexes in cells devoid of full-length protein
    Hanna Laudon
    Karolinska Institutet, Neurotec, Section for Experimental Geriatrics, Novum, Huddinge, Sweden
    J Neurochem 89:44-53. 2004
    ..Taken together, our findings indicate that ectopically expressed NTF and CTF restore functional gamma-secretase complexes and that the presence of full-length PS1 is not a requirement for proper complex assembly...
  76. pmc In vivo reduction of amyloid-beta by a mutant copper transporter
    Amie L Phinney
    Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2
    Proc Natl Acad Sci U S A 100:14193-8. 2003
    ..These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide...
  77. ncbi request reprint App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome
    Anne M Cataldo
    Mailman Research Center, McLean Hospital, Belmont, Massachusetts 02478, USA
    J Neurosci 23:6788-92. 2003
    ..These results identify an essential role for App gene triplication in causing AD-related endosomal abnormalities and further establish the pathogenic significance of endosomal dysfunction in AD...
  78. ncbi request reprint Setback for an Alzheimer's disease vaccine: lessons learned
    Paul M Mathews
    Neurology 61:7-8. 2003
  79. ncbi request reprint Alzheimer's presenilin 1 modulates sorting of APP and its carboxyl-terminal fragments in cerebral neurons in vivo
    Sam Gandy
    Farber Institute for Neurosciences and the Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    J Neurochem 102:619-26. 2007
    ..The chimera experiment suggests that TGN-enrichment of a beta-/gamma-secretase substrate may play an integral role in the action of mutant PS1 to elevate brain levels of Abeta42...
  80. pmc Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype
    Richard Rozmahel
    Center for Research in Neurodegenerative Diseases, Department of Pharmacology, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 99:14452-7. 2002
    ..The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease...
  81. pmc Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
    Daniel J Klionsky
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Autophagy 4:151-75. 2008
    ..In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response...
  82. ncbi request reprint Autophagy and its possible roles in nervous system diseases, damage and repair
    David C Rubinsztein
    Departments of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge, UK
    Autophagy 1:11-22. 2005
    ..While many issues remain unresolved, these conditions raise the possibility that autophagy can have either deleterious or protective effects depending on the specific situation and stage in the pathological process...
  83. ncbi request reprint Neuronal macroautophagy: from development to degeneration
    Barry Boland
    Department of Pharmacology, Oxford University, Oxford OX13QT, United Kingdom
    Mol Aspects Med 27:503-19. 2006
    ....

Research Grants9

  1. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph A Nixon; Fiscal Year: 2010
    ....
  2. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph Nixon; Fiscal Year: 2003
    ....
  3. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph Nixon; Fiscal Year: 2005
    ....
  4. LASER SCANNING CONFOCAL MICROSCOPE
    Ralph Nixon; Fiscal Year: 2005
    ....
  5. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph Nixon; Fiscal Year: 2002
    ....
  6. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph Nixon; Fiscal Year: 2004
    ....
  7. DYNAMICS OF THE NEURONAL CYTOSKELETON IN AGING BRAIN
    Ralph Nixon; Fiscal Year: 2006
    ....