alpha synuclein

Summary

Gene Symbol: alpha synuclein
Description: synuclein alpha
Alias: NACP, PARK1, PARK4, PD1, alpha-synuclein, non A-beta component of AD amyloid, synuclein alpha-140, synuclein, alpha (non A4 component of amyloid precursor)
Species: human

Top Publications

  1. pmc Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein
    Paula Desplats
    Department of Neurosciences and Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:13010-5. 2009
  2. pmc α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation
    Tim Bartels
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 477:107-10. 2011
  3. pmc Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease
    Todd L Edwards
    John P Hussman Institute for Human Genomics, University of Miami, FL 33136, USA
    Ann Hum Genet 74:97-109. 2010
  4. pmc Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis
    Venu M Nemani
    Departments of Neurology and Physiology, Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA
    Neuron 65:66-79. 2010
  5. pmc Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies
    Joseph R Mazzulli
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Cell 146:37-52. 2011
  6. pmc Genomewide association study for susceptibility genes contributing to familial Parkinson disease
    Nathan Pankratz
    Indiana University School of Medicine, Health Information and Translational Sciences Building, Indianapolis, IN 46202 3002, USA
    Hum Genet 124:593-605. 2009
  7. pmc Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21
    Chris C A Spencer
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Hum Mol Genet 20:345-53. 2011
  8. pmc Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies
    David J Irwin
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer s Disease Core Center, Institute on Aging, University of Pennsylvania Perelman School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 14:626-36. 2013
  9. pmc Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro
    Jacqueline Burré
    Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304 5543, USA
    Science 329:1663-7. 2010
  10. ncbi Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct
    K A Conway
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Science 294:1346-9. 2001

Research Grants

  1. NIKOLAUS RENZ MCFARLAND; Fiscal Year: 2014
  2. Role of oligomeric alpha-synuclein in synucleinopathies
    Pamela J McLean; Fiscal Year: 2013
  3. NEUROPATHOLOGY OF CHRONIC MANGANESE EXPOSURE
    Brad A Racette; Fiscal Year: 2010
  4. Paula C Bickford; Fiscal Year: 2016
  5. GI Endotoxin as an Environmental Trigger in an alpha-Synuclein Transgenic Mouse
    Robert L Nussbaum; Fiscal Year: 2012
  6. Mechanisms of Selective Neurodegeneration in Parkinson Disease
    Xugang Xia; Fiscal Year: 2010
  7. The Role of Lysosomal Dysfunction in Parkinson Disease-Related Neurodegeneration
    LAUREN REBECCA KETT; Fiscal Year: 2013
  8. JADA M LEWIS; Fiscal Year: 2016
  9. Role of complement in alpha-synuclein based models of Parkinson disease
    HEATHER ELIZABETH ALLEN; Fiscal Year: 2013
  10. Cellular Mechanisms of Neuropathology in Parkinson's Disease
    John J Shacka; Fiscal Year: 2013

Detail Information

Publications387 found, 100 shown here

  1. pmc Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein
    Paula Desplats
    Department of Neurosciences and Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 106:13010-5. 2009
    ..These findings demonstrate the cell-to-cell transmission of alpha-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies...
  2. pmc α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation
    Tim Bartels
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 477:107-10. 2011
    ....
  3. pmc Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease
    Todd L Edwards
    John P Hussman Institute for Human Genomics, University of Miami, FL 33136, USA
    Ann Hum Genet 74:97-109. 2010
    ..79] T vs. C allele, PAR%= 8%) were genome-wide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD...
  4. pmc Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis
    Venu M Nemani
    Departments of Neurology and Physiology, Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA
    Neuron 65:66-79. 2010
    ..Increased levels of alpha-synuclein thus produce a specific, physiological defect in synaptic vesicle recycling that precedes detectable neuropathology...
  5. pmc Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies
    Joseph R Mazzulli
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA
    Cell 146:37-52. 2011
    ..Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies...
  6. pmc Genomewide association study for susceptibility genes contributing to familial Parkinson disease
    Nathan Pankratz
    Indiana University School of Medicine, Health Information and Translational Sciences Building, Indianapolis, IN 46202 3002, USA
    Hum Genet 124:593-605. 2009
    ..8 x 10(-6); additive model: p = 4.8 x 10(-5)). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility...
  7. pmc Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21
    Chris C A Spencer
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Hum Mol Genet 20:345-53. 2011
    ..We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease...
  8. pmc Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies
    David J Irwin
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer s Disease Core Center, Institute on Aging, University of Pennsylvania Perelman School of Medicine, HUP, Maloney 3rd Floor, 36th and Spruce Streets, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 14:626-36. 2013
    ..An understanding of the relationships between these three distinct pathologies and their resultant clinical phenotypes is crucial for the development of effective disease-modifying treatments for PD and PDD. ..
  9. pmc Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro
    Jacqueline Burré
    Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304 5543, USA
    Science 329:1663-7. 2010
    ..Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging...
  10. ncbi Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct
    K A Conway
    Center for Neurologic Diseases, Brigham and Women s Hospital, Department of Neurology, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Science 294:1346-9. 2001
    ..Adduct formation provides an explanation for the dopaminergic selectivity of alpha-synuclein-associated neurotoxicity in PD and has implications for current and future PD therapeutic and diagnostic strategies...
  11. ncbi Mutation in the alpha-synuclein gene identified in families with Parkinson's disease
    M H Polymeropoulos
    Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 1430, USA
    Science 276:2045-7. 1997
    ..This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder...
  12. pmc Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration
    Hui Ming Gao
    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 28:7687-98. 2008
    ..This study advances understanding of the role of neuroinflammation and abnormal SYN in the pathogenesis of PD and opens new avenues for the discovery of more effective therapies for PD...
  13. ncbi Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease
    Demetrius M Maraganore
    Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA
    JAMA 296:661-70. 2006
    ..Alpha-synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking...
  14. pmc Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons
    Martin Lundblad
    Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund 221 84, Sweden
    Proc Natl Acad Sci U S A 109:3213-9. 2012
    ..Synaptic dysfunction and axonopathy would thus be the hallmark of presymptomatic and early-stage Parkinson disease, followed by neuronal degeneration and cell loss, characteristic of more advanced stages of the disease...
  15. ncbi Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation
    L Narhi
    Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    J Biol Chem 274:9843-6. 1999
    ..These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations...
  16. pmc Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 31:763-80. 2010
    ....
  17. ncbi Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies
    E Kuusisto
    1Department of Neuroscience and Neurology, Section of Neuropathology, University of Kuopio, P O Box 1627, FIN 70211 Kuopio, Finland
    Neuroreport 12:2085-90. 2001
    ....
  18. doi Prion-like acceleration of a synucleinopathy in a transgenic mouse model
    Anne Laure Mougenot
    Anses, Laboratoire de Lyon, Unité Maladies Neurodégénératives, Lyon, France
    Neurobiol Aging 33:2225-8. 2012
    ....
  19. ncbi Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism
    Tetyana Duka
    Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Washington, DC, USA
    FASEB J 20:2302-12. 2006
    ....
  20. pmc Axonopathy in an α-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated α-synuclein
    Dora Games
    Neotope Biosciences, South San Francisco, California, USA
    Am J Pathol 182:940-53. 2013
    ..These results show that neuritic dystrophy is a prominent pathologic feature of the mThy1-α-syn tg model and suggest that CT α-syn might play an important role in the process of axonal damage in these mice as well as in DLB and PD...
  21. pmc Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain
    Latha Devi
    Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA
    J Biol Chem 283:9089-100. 2008
    ..These results provide evidence that mitochondrial accumulated alpha-synuclein may interact with complex I and interfere with its functions...
  22. ncbi Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration
    Sreeganga Chandra
    Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell 123:383-96. 2005
    ....
  23. pmc Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
    Valerie Cullen
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Brain 2:5. 2009
    ..To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD), on aSyn processing...
  24. doi Quantification of α-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies
    Brit Mollenhauer
    Paracelsus Elena Klinik, Kassel, Klinikstrasse 16, 34128 Kassel, Germany
    Biomark Med 4:683-99. 2010
    ..We also provide specific information regarding standardized operating procedures for cerebrospinal fluid collection in PD biomarker research efforts...
  25. pmc The Parkinson's disease protein alpha-synuclein disrupts cellular Rab homeostasis
    Aaron D Gitler
    Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 105:145-50. 2008
    ..Thus, alpha-syn causes general defects in vesicle trafficking, to which dopaminergic neurons are especially sensitive...
  26. pmc α-Synuclein oligomers and clinical implications for Parkinson disease
    Lorraine V Kalia
    Morton and Gloria Shulman Movement Disorders Centre and Edmond J Safra Program in Parkinson s Disease, Toronto Western Hospital, Toronto, Ontario, Canada
    Ann Neurol 73:155-69. 2013
    ..Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications...
  27. pmc Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
    Alexis Elbaz
    INSERM, U708, Neuroepidemiology, F 75013, Paris, France
    Ann Neurol 69:778-92. 2011
    ....
  28. pmc Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson's disease brains with and without dementia
    Jonathan Wills
    Department of Biochemistry and Molecular and Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA
    Exp Neurol 225:210-8. 2010
    ....
  29. ncbi alpha-Synuclein locus triplication causes Parkinson's disease
    A B Singleton
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 302:841. 2003
  30. doi Assembly-dependent endocytosis and clearance of extracellular alpha-synuclein
    He Jin Lee
    Institute of Biomedical Science and Technology, Konkuk University, Seoul 143 701, Republic of Korea
    Int J Biochem Cell Biol 40:1835-49. 2008
    ....
  31. ncbi Neurological and neurodegenerative alterations in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy
    Clifford W Shults
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093 0624, USA
    J Neurosci 25:10689-99. 2005
    ..Together, these studies support the contention that accumulation of alpha-syn in oligodendrocytes promotes neurodegeneration and recapitulates several of the key functional and neuropathological features of MSA...
  32. pmc Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease
    Shaji Theodore
    Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Alabama 35294 0021, USA
    J Neuropathol Exp Neurol 67:1149-58. 2008
    ..These data show that overexpression of alpha-SYN alone, in the absence of overt neurodegeneration, is sufficient to trigger neuroinflammation with both microglial activation and stimulation of adaptive immunity...
  33. pmc Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models
    Tetyana Duka
    Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia, USA
    FASEB J 23:2820-30. 2009
    ..These data unveil a previously unappreciated role of alpha-Syn in the induction of p-GSK-3beta, and demonstrate the importance of this kinase in the genesis and maintenance of neurodegenerative changes associated with PD...
  34. pmc Sumoylation inhibits alpha-synuclein aggregation and toxicity
    Petranka Krumova
    Department of Neurology and 2 Department of Biochemistry I, University of Gottingen, 37073 Gottingen, Germany
    J Cell Biol 194:49-60. 2011
    ..These findings strongly support the model that sumoylation promotes protein solubility and suggest that defects in sumoylation may contribute to aggregation-induced diseases...
  35. doi Single particle characterization of iron-induced pore-forming alpha-synuclein oligomers
    Marcus Kostka
    CNS Research, Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Birkendorferstrasse 65, 88397 Biberach, Germany
    J Biol Chem 283:10992-1003. 2008
    ..Moreover, scanning for intensely fluorescent targets allows high throughput screening for aggregation inhibitors and may provide new approaches for drug development and therapy...
  36. pmc SNCA variant associated with Parkinson disease and plasma alpha-synuclein level
    Ignacio F Mata
    Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Mailstop S 182, 1660 S Columbian Way, Seattle, WA 98108, USA
    Arch Neurol 67:1350-6. 2010
    ..A functional repeat polymorphism in the SNCA promoter (REP1) conveys susceptibility for Parkinson disease (PD). There is also increasing evidence that single-nucleotide polymorphisms (SNPs) elsewhere in the gene are associated with PD risk...
  37. pmc Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α-synuclein
    Darius Ebrahimi-Fakhari
    Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 31:14508-20. 2011
    ..These results provide a novel link between the UPS, the ALP, and α-synuclein pathology and may have important implications for future therapeutics targeting degradation pathways...
  38. pmc Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein
    Carlos W Bertoncini
    Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D 37077 Gottingen, Germany
    Proc Natl Acad Sci U S A 102:1430-5. 2005
    ..Stabilization of the native, autoinhibitory structure of alphaS constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson's disease...
  39. pmc Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1
    Frits Kamp
    DZNE German Center for Neurodegenerative Diseases, Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
    EMBO J 29:3571-89. 2010
    ..Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin Δ1-79 or by DJ-1 C106A...
  40. ncbi Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease
    P Ibanez
    INSERM U289, Neurologie et Thérapeutique Expérimentale, Hopital de la Pitie Salpetriere, AP HP, Paris, France
    Lancet 364:1169-71. 2004
    ..These results indicate that SNCA is more frequently associated with familial Parkinson's disease than previously thought, and that there is a clear dosage effect according to the number of supernumerary copies of this gene...
  41. pmc Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary Parkinsonism
    Cecile Martinat
    Department of Pathology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, New York, New York, USA
    PLoS Biol 2:e327. 2004
    ..These data are consistent with a protective role for DJ-1, and demonstrate the utility of genetically modified embryonic stem cell-derived neurons as cellular models of neuronal disorders...
  42. doi Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss?
    Annika Ohrfelt
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden
    Neurosci Lett 450:332-5. 2009
    ..The lower alpha-syn levels in AD, as well as the association of alpha-syn reduction with AD severity, approximated by MMSE, suggests that it may be a general marker of synapse loss, a hypothesis that warrants further investigation...
  43. ncbi Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death
    Lee J Martin
    Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 2196, USA
    J Neurosci 26:41-50. 2006
    ..Thus, A53T mutant mice develop intraneuronal inclusions, mitochondrial DNA damage and degeneration, and apoptotic-like death of neocortical, brainstem, and motor neurons...
  44. doi Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein
    Franz Marxreiter
    Department of Neurology, University of Regensburg, Universitatsstrasse 84, 93053 Regensburg, Germany
    Eur J Neurosci 29:879-90. 2009
    ..This finding suggests that interfering with alpha-synuclein pathology can rescue newly generated neurons, possibly leading to new targets for therapeutic interventions in synucleinopathies...
  45. pmc Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease
    Rodolfo M Rasia
    Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany
    Proc Natl Acad Sci U S A 102:4294-9. 2005
    ..The metallobiology of Cu(II) in Parkinson's disease is discussed by a comparative analysis with other Cu(II)-binding proteins involved in neurodegenerative disorders...
  46. pmc Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Neurosci 31:7604-18. 2011
    ..The current work not only provides an exceptional cellular model of tau pathology, but also examines α-syn-induced tau inclusion formation and provides novel insights into hyperphosphorylation observed in disease...
  47. pmc Genomic investigation of alpha-synuclein multiplication and parkinsonism
    Owen A Ross
    Division of Neurogenetics, Department of Neuroscience, College of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA
    Ann Neurol 63:743-50. 2008
    ..Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the alpha-synuclein gene (SNCA)...
  48. doi Phosphorylation does not prompt, nor prevent, the formation of alpha-synuclein toxic species in a rat model of Parkinson's disease
    Samareh Azeredo da Silveira
    Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Hum Mol Genet 18:872-87. 2009
    ....
  49. doi Mitochondrial association of alpha-synuclein causes oxidative stress
    M S Parihar
    Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University, 460 West 12th Avenue, Columbus, 43210 OH, USA
    Cell Mol Life Sci 65:1272-84. 2008
    ..These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein...
  50. pmc Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formation
    Li Chen
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 119:3257-65. 2009
    ....
  51. ncbi Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system
    O Chiba-Falek
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive, MSC 4472, Bethesda, MD 20892 4472, USA
    Hum Mol Genet 10:3101-9. 2001
    ..been implicated in familial Parkinson's disease (PD) while certain polymorphic alleles at a microsatellite repeat, NACP-Rep1, located approximately 10 kb upstream of the gene, have been associated with sporadic PD...
  52. ncbi Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred
    John E Duda
    Parkinson s Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Pennsylvania, USA
    Acta Neuropathol 104:7-11. 2002
    ..We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains...
  53. pmc Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease
    Katrina L Paumier
    Neuroscience Research Unit, Pfizer Global Research and Development, Cambridge, Massachusetts, USA
    PLoS ONE 8:e70274. 2013
    ..Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments similar to PD patients and may provide useful endpoints for assessing novel therapeutic interventions for PD. ..
  54. pmc Single molecule characterization of α-synuclein in aggregation-prone states
    Adam J Trexler
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
    Biophys J 99:3048-55. 2010
    ..Binding of these molecules gives rise to only minor conformational changes in αS, suggesting that their mechanism of aggregation enhancement is fundamentally different from that of low pH...
  55. ncbi Alpha-synuclein has a high affinity for packing defects in a bilayer membrane: a thermodynamics study
    Brigitte Nuscher
    Department of Biochemistry, Ludwig Maximilian University, 80336 Munich, Germany
    J Biol Chem 279:21966-75. 2004
    ..This will be discussed with regard to a possible role of the protein for the stabilization of synaptic vesicle membranes...
  56. ncbi Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and alpha-synuclein
    Veronique Dorval
    Department of Medical Biophysics and Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 281:9919-24. 2006
    ..These findings revealed a new, possibly regulatory, modification of tau and alpha-synuclein that may also have implications for their pathogenic roles in neurodegenerative diseases...
  57. pmc Mapping the subcellular distribution of α-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: implications for Parkinson's disease pathogenesis
    Daniela Boassa
    National Center for Microscopy and Imaging Research and Center for Research on Biological Systems, University of California, San Diego, La Jolla, California 92093, USA
    J Neurosci 33:2605-15. 2013
    ..Our data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation...
  58. pmc Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity
    Aaron D Gitler
    Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, Cambridge, Massachusetts 02142, USA
    Nat Genet 41:308-15. 2009
    ..Finally, we show that additional genes from our yeast screen, with diverse functions, are potent modifiers of alpha-syn-induced neuron loss in animals, establishing a diverse, highly conserved interaction network for alpha-syn...
  59. ncbi Analyses of copy number and mRNA expression level of the alpha-synuclein gene in multiple system atrophy
    Honglian Jin
    Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku 113 8519, Tokyo, Japan
    J Med Dent Sci 55:145-53. 2008
    ..However, GCIs were seen in these MSA specimens on immunohistochemistry for alpha-synuclein. These results suggest that alpha-synuclein gene expression is not the fundamental cause of MSA...
  60. doi PLK2 modulates α-synuclein aggregation in yeast and mammalian cells
    Elisa Basso
    Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisbon, Portugal
    Mol Neurobiol 48:854-62. 2013
    ..Our study supports a role for PLK2 in the generation of aSyn inclusions by a mechanism that does not depend directly on serine 129 phosphorylation...
  61. ncbi Defective membrane interactions of familial Parkinson's disease mutant A30P alpha-synuclein
    Euijung Jo
    Centre for Research in Neurodegenerative Diseases, 6 Queen s Park Crescent West, Toronto, Ontario, M5S 3H2, Canada
    J Mol Biol 315:799-807. 2002
    ..With these observations, we suggest that the A53T and A30P mutants may have different physiological consequences in vivo and could possibly contribute to early onset Parkinson's disease via unique mechanisms...
  62. pmc Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo
    Abid Oueslati
    Laboratory of Molecular and Chemical Biology of Neurodegeneration and Neurodegenerative Disease Laboratory, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Proc Natl Acad Sci U S A 110:E3945-54. 2013
    ..Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of α-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies. ..
  63. ncbi Alpha-synuclein is expressed in different tissues during human fetal development
    Svetlana Ltic
    Institute for Biological Research, Belgrade, Serbia and Montenegro
    J Mol Neurosci 22:199-204. 2004
    ..These findings suggest that apart from its function in development of the nervous system, alpha-synuclein has an important function in peripheral tissues as well during normal human prenatal development...
  64. pmc Alpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo
    Elodie Angot
    Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
    PLoS ONE 7:e39465. 2012
    ..Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology...
  65. ncbi beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor
    M Hashimoto
    Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
    Neuron 32:213-23. 2001
    ..Such an anti-amyloidogenic property of beta-synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders...
  66. pmc Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma
    Yasuhiro Matsuo
    Department of Medicine, Center for Molecular Chaperone Radiobiology and Cancer Virology, Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America
    PLoS ONE 5:e10481. 2010
    ..Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components...
  67. pmc Accumulation of toxic α-synuclein oligomer within endoplasmic reticulum occurs in α-synucleinopathy in vivo
    Emanuela Colla
    Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 32:3301-5. 2012
    ..These results indicate that αS oligomers with toxic conformation accumulate in ER, and αS oligomer-dependent ER stress is pathologically relevant for PD...
  68. pmc Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells
    Tereza Vogiatzi
    Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Soranou Efesiou 4, Athens, Greece
    J Biol Chem 283:23542-56. 2008
    ..These results indicate that CMA and macroautophagy are important pathways for WT ASYN degradation in neurons and underline the importance of CMA as degradation machinery in the nervous system...
  69. pmc Heat-shock protein 70 modulates toxic extracellular α-synuclein oligomers and rescues trans-synaptic toxicity
    Karin M Danzer
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, 114 16th St, Charlestown, MA 02129, USA
    FASEB J 25:326-36. 2011
    ....
  70. pmc Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein
    Katerina E Paleologou
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    J Biol Chem 283:16895-905. 2008
    ....
  71. ncbi Proteasomal inhibition by alpha-synuclein filaments and oligomers
    Evo Lindersson
    Department of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark
    J Biol Chem 279:12924-34. 2004
    ..The inhibitory effect of amyloid aggregates may thus be amenable to modulation by endogenous chaperones and possibly accessible for therapeutic intervention...
  72. pmc Neurodegenerative phenotypes in an A53T α-synuclein transgenic mouse model are independent of LRRK2
    João Paulo L Daher
    Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Hum Mol Genet 21:2420-31. 2012
    ..These observations fail to provide support for a pathophysiological interaction of LRRK2 and α-synuclein in vivo, at least within neurons of the mouse hindbrain...
  73. pmc Systematic mutagenesis of α-synuclein reveals distinct sequence requirements for physiological and pathological activities
    Jacqueline Burré
    Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 5453, USA
    J Neurosci 32:15227-42. 2012
    ....
  74. ncbi Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease
    Pavan K Auluck
    Department of Neuroscience, University of Pennsylvania and University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 295:865-8. 2002
    ..Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression...
  75. pmc Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling
    Tziona Ben Gedalya
    Department of Cellular Biochemistry and Human Genetics, Faculty of Medicine, Hebrew University, Ein Kerem, Jerusalem 91120, Israel
    Traffic 10:218-34. 2009
    ..We suggest that alphaS and PUFAs normally function in endocytic mechanisms and are specifically involved in SV recycling upon neuronal stimulation...
  76. pmc Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy
    Ammar Al-Chalabi
    MRC Centre for Neurodegeneration Research, King s College London, Department of Clinical Neuroscience, Institute of Psychiatry, and NIHR Biomedical Research Centre, London, United Kingdom
    PLoS ONE 4:e7114. 2009
    ..Genetic variants of the alpha-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson's disease has identified association of a SNP in SNCA with MSA...
  77. pmc Molecular mechanisms of alpha-synuclein neurodegeneration
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
    Biochim Biophys Acta 1792:616-24. 2009
    ..In this review, some of the evidence for the different mechanisms of alpha-synuclein toxicity is presented and discussed...
  78. ncbi Tau and alpha-synuclein in susceptibility to, and dementia in, Parkinson's disease
    An Goris
    Department of Clinical Neurosciences Neurology Unit, University of Cambridge, Cambridge, United Kingdom
    Ann Neurol 62:145-53. 2007
    ..We investigated the genetic basis of susceptibility to and cognitive heterogeneity of this disease...
  79. pmc Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model
    Shusei Hamamichi
    Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA
    Proc Natl Acad Sci U S A 105:728-33. 2008
    ..These data represent putative genetic susceptibility loci and potential therapeutic targets for PD, a movement disorder affecting approximately 2% of the population over 65 years of age...
  80. pmc Behavioral effects of dopaminergic agonists in transgenic mice overexpressing human wildtype alpha-synuclein
    S M Fleming
    Department of Neurology and Neurobiology, The David Geffen School of Medicine at the University of California Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095 1769, USA
    Neuroscience 142:1245-53. 2006
    ..In contrast to wild-type mice, Thy1-aSyn mice did not show amphetamine-induced stereotypies. The results indicate that chronic overexpression of alpha-synuclein led to abnormal pharmacological responses in mice...
  81. doi Characterizing the dynamics of α-synuclein oligomers using hydrogen/deuterium exchange monitored by mass spectrometry
    Simon Mysling
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark
    Biochemistry 52:9097-103. 2013
    ..This region has mainly been described in relation to membrane binding of αSN, and structuring may be important in relation to disease. ..
  82. pmc Solid-state ¹³C NMR reveals annealing of raft-like membranes containing cholesterol by the intrinsically disordered protein α-Synuclein
    Avigdor Leftin
    Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA
    J Mol Biol 425:2973-87. 2013
    ..We propose this process is implicated in regulation of synaptic membrane fusion that may be altered by aggregation of αS in Parkinson's disease...
  83. doi α-Synuclein and protein degradation systems: a reciprocal relationship
    Maria Xilouri
    Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens BRFAA, 4 Soranou Efesiou Street, Athens 11527, Greece
    Mol Neurobiol 47:537-51. 2013
    ..Identifying the factors that regulate alpha-synuclein association to cellular proteolytic pathways may represent potential targets for therapeutic interventions in PD and related synucleinopathies...
  84. doi Impaired olfactory bulb neurogenesis depends on the presence of human wild-type alpha-synuclein
    V E L May
    Department of Molecular Neurology, Friedrich Alexander University of Erlangen Nurnberg, Erlangen, Germany
    Neuroscience 222:343-55. 2012
    ..Thus, our study further contributes insights into α-syn accumulation as a causative player in the impairment of adult neurogenesis and emphasizes its diverse role in cell renewal of distinct OB cell layers...
  85. pmc Impairment of mitochondria in adult mouse brain overexpressing predominantly full-length, N-terminally acetylated human α-synuclein
    Theodore A Sarafian
    Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America
    PLoS ONE 8:e63557. 2013
    ..Overall the study showed that accumulation of full-length, N-terminally acetylated human α-synuclein was sufficient to disrupt brain mitochondrial function in adult mice...
  86. ncbi Alpha-synuclein up-regulation and aggregation during MPP+-induced apoptosis in neuroblastoma cells: intermediacy of transferrin receptor iron and hydrogen peroxide
    Shasi V Kalivendi
    Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Biol Chem 279:15240-7. 2004
    ..We conclude that MPP(+)-induced iron signaling is responsible for intracellular oxidant generation, alpha-syn expression, proteasomal dysfunction, and apoptosis. Relevance to Parkinson's disease is discussed...
  87. ncbi The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways
    Youngah Shin
    Alzheimer Disease Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:23727-34. 2005
    ..Taken together, these data suggest that CHIP acts a molecular switch between proteasomal and lysosomal degradation pathways...
  88. pmc Inhibition of alpha-synuclein fibrillization by dopamine is mediated by interactions with five C-terminal residues and with E83 in the NAC region
    Fernando E Herrera
    International School for Advanced Studies SISSA, INFM DEMOCRITOS, Trieste, Italy
    PLoS ONE 3:e3394. 2008
    ..In contrast, and consistent with our modeling studies, the replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit AS fibrillization...
  89. doi Role of post-translational modifications in modulating the structure, function and toxicity of alpha-synuclein: implications for Parkinson's disease pathogenesis and therapies
    Abid Oueslati
    Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, The Ecole Polytechnique Fédérale de Lausanne EPFL, Lausanne, Switzerland
    Prog Brain Res 183:115-45. 2010
    ..Furthermore, the identification of the natural enzymes involved in regulating the post-translational modifications of alpha-synuclein will yield novel and more tractable therapeutic targets to treat PD and related synucleinopathies...
  90. pmc Role of alpha-synuclein protein levels in mitochondrial morphology and cell survival in cell lines
    Min Zhu
    Laboratory for Neurology of Institute of Integrative Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, PR China
    PLoS ONE 7:e36377. 2012
    ..These data suggest that α-synuclein protein levels hardly affect mitochondrial morphology in normal cell lines, but may have some influence on that under certain environmental conditions...
  91. pmc Resistance to MPTP-neurotoxicity in α-synuclein knockout mice is complemented by human α-synuclein and associated with increased β-synuclein and Akt activation
    Bobby Thomas
    Neuroregeneration and Stem Cell Programs, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 6:e16706. 2011
    ..Together these findings provide new mechanistic insights on the role α-synuclein in modulating neurodegenerative phenotypes by regulation of Akt-mediated cell survival signaling in vivo...
  92. pmc The A53T mutation is key in defining the differences in the aggregation kinetics of human and mouse α-synuclein
    Lijuan Kang
    Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, New Jersey 08854, United States
    J Am Chem Soc 133:13465-70. 2011
    ....
  93. doi Stimulatory effect of α-synuclein on the tau-phosphorylation by GSK-3β
    Fumitaka Kawakami
    Department of Biochemistry, Kitasato University, Minami Ku, Sagamihara, Japan
    FEBS J 278:4895-904. 2011
    ..These results suggest that the cellular level of Hsp70 may be a novel therapeutic target to counteract α-SN-mediated tau phosphorylation in the initial stage of neurodegenerative disease...
  94. doi The conformation and the aggregation kinetics of α-synuclein depend on the proline residues in its C-terminal region
    Jessika Meuvis
    Laboratory of Biomolecular Dynamics, Katholieke Universiteit Leuven, Celestijnenlaan 200G, Leuven, Belgium
    Biochemistry 49:9345-52. 2010
    ....
  95. ncbi Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling
    Ani Der-Sarkissian
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90089, USA
    J Biol Chem 278:37530-5. 2003
    ..Although the lengths of the respective core regions differ, fibrils from different amyloid proteins nevertheless appear to be able to take up highly similar, and possibly conserved, structures...
  96. pmc α-Synuclein: the long distance runner
    Sonia George
    Neuronal Survival Unit, Wallenberg Neuroscience Center, Lund University, Lund, Sweden
    Brain Pathol 23:350-7. 2013
    ..We describe recent studies investigating cell-to-cell transfer of α-synuclein and focus our review on the long-distance axonal transport of α-synuclein along neurons...
  97. pmc At low concentrations, 3,4-dihydroxyphenylacetic acid (DOPAC) binds non-covalently to alpha-synuclein and prevents its fibrillation
    Wenbo Zhou
    Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, CA 95064, USA
    J Mol Biol 388:597-610. 2009
    ....
  98. pmc Beta-synuclein gene alterations in dementia with Lewy bodies
    H Ohtake
    Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
    Neurology 63:805-11. 2004
    ..To determine whether mutations in the genes for alpha-synuclein or beta-synuclein are responsible for dementia with Lewy bodies (DLB), a disorder closely related to Parkinson disease (PD)...
  99. ncbi Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression
    Yuxin Fan
    Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USA
    Hum Mol Genet 15:3002-11. 2006
    ..As increased expression of alpha-synuclein may cause or contribute to PD pathogenesis in sporadic and familial forms of disease, this observation has important implications for the development of therapies for PD...
  100. pmc Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human α-synuclein
    Hoa A Lam
    Hatos Center, University of California Los Angeles, Los Angeles, California, USA
    J Neurosci Res 89:1091-102. 2011
    ..Together, these data further validate this transgenic mouse line as a slowly progressing model of Parkinson's disease and provide evidence for early dopamine synaptic dysfunction prior to loss of striatal dopamine...
  101. pmc Alterations in corticostriatal synaptic plasticity in mice overexpressing human alpha-synuclein
    J B Watson
    Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Neuroscience 159:501-13. 2009
    ..ASOTg mice may recapitulate an early stage in PD during which overexpressed alpha-synuclein dampens corticostriatal synaptic transmission and reduces movement...

Research Grants71

  1. NIKOLAUS RENZ MCFARLAND; Fiscal Year: 2014
    ..Developing these research skills, along with my continued clinical training and experience are critical to becoming a successful, independent clinician-scientist committed to translational neuroscience. ..
  2. Role of oligomeric alpha-synuclein in synucleinopathies
    Pamela J McLean; Fiscal Year: 2013
    ..The goals of the current application are to understand 1syn oligomer formation and how it relates to disease development in humans and to further explore factors that modify and rescue 1syn aggregation. ..
  3. NEUROPATHOLOGY OF CHRONIC MANGANESE EXPOSURE
    Brad A Racette; Fiscal Year: 2010
    ..Findings from this study may be translated into preventative measures to reduce the frequency of Parkinson disease. ..
  4. Paula C Bickford; Fiscal Year: 2016
    ..If these therapies have significant clinical potential this will be a step forward for Parkinsons therapeutics. ..
  5. GI Endotoxin as an Environmental Trigger in an alpha-Synuclein Transgenic Mouse
    Robert L Nussbaum; Fiscal Year: 2012
    ..By understanding the disease process, we can identify points at which interventions could slow or stop its progression. ..
  6. Mechanisms of Selective Neurodegeneration in Parkinson Disease
    Xugang Xia; Fiscal Year: 2010
    ..The results from these studies would advance the understanding on the disease mechanisms and would guide the development of PD therapy. ..
  7. The Role of Lysosomal Dysfunction in Parkinson Disease-Related Neurodegeneration
    LAUREN REBECCA KETT; Fiscal Year: 2013
    ..These results will contribute more broadly to understanding the role of the lysosome in PD pathogenesis. ..
  8. JADA M LEWIS; Fiscal Year: 2016
    ....
  9. Role of complement in alpha-synuclein based models of Parkinson disease
    HEATHER ELIZABETH ALLEN; Fiscal Year: 2013
    ..First, we will determine whether alpha synuclein can lead to complement activation in our AAV-SYN mouse model of PD...
  10. Cellular Mechanisms of Neuropathology in Parkinson's Disease
    John J Shacka; Fiscal Year: 2013
    ..is a leading age-related neurodegenerative disease and our laboratory studies the mechanisms by which toxic alpha synuclein species accumulate in PD and contribute to PD neuropathology and neurodegeneration...
  11. Eugene V Mosharov; Fiscal Year: 2015
    ....
  12. Dimitri Krainc; Fiscal Year: 2015
    ....
  13. Alpha-Synuclein-Metal Complexes and Oxidative Stress in Parkinson's Disease
    Feimeng Zhou; Fiscal Year: 2012
    ..Furthermore, given the variety of techniques proposed and the interdisciplinary nature of this high-impact research, the work will play a significant part in training the next generation of researchers at a minority-serving institution. ..
  14. Novel mechanism of neuroprotection against neurotoxins
    Jianhua Zhang; Fiscal Year: 2012
    ..We will study the effect of partial loss-of-function and gain-of- function of a lysosomal enzyme in Parkinson's disease models. This study will help establish lysosomal based therapy for Parkinson's disease. ..
  15. Alpha-synuclein RNAi in a model of sporadic Parkinson's disease
    EDWARD ALAN BURTON; Fiscal Year: 2012
    ..abstract_text> ..
  16. Characterization of the role of cyclin G-associated kinase in Parkinson disease
    Richard H Myers; Fiscal Year: 2013
    ..These PD investigators are uniquely experienced with the GAK gene and region and have already in hand all the samples needed to carry out these definitive studies. ..
  17. Alpha-Synuclein Isomers as Novel Immunogens for Immunotherapy of Parkinsons Disea
    ROWEN JY CHANG; Fiscal Year: 2010
    ..Successful completion of this project will generate lead aSyn isomers, effective in PD transgenic mouse model, for further development as therapeutic vaccine in treatment of PD. ..
  18. William A Wolf; Fiscal Year: 2014
    ..Another prominent factor in the pathogenesis of PD is the protein, alpha synuclein (ASyn), but again its precise involvement is unclear...
  19. Gene-environment interactions in transgenic rat models of Parkinson disease
    J Timothy Greenamyre; Fiscal Year: 2010
    ..As such, we will begin to define the relationship between a known environmental risk factor and identified genetic risk factors in the causation of this devastating illness. ..
  20. MGH/MIT MORRIS UDALL CENTER OF EXCELLENCE IN PD RESEARCH
    Anne Young; Fiscal Year: 2009
    ..The investigators of the MGH/MIT Center are dedicated to a program of collaborative and interactive studies which will lead to better treatments for people with Parkinson's disease. ..
  21. Metal-Induced Structural Transformations during Alpha-Synuclein Aggregation.
    Lia Stanciu; Fiscal Year: 2012
    ....
  22. The Roles of a-Synuclein and Parkin in Parkinson Disease
    Michael Schlossmacher; Fiscal Year: 2005
    ..Rare heritable forms of PD are linked to an increasing number of gene loci. At the PARK1 locus, SNCA encodes a neuronal protein, alpha-synuclein (alpha-S), that is involved in the transition of synaptic ..
  23. Structure and conformational dynamics of alpha-synuclein
    QUYEN QUOC HOANG; Fiscal Year: 2013
    ..We will do so by using a combination of X-ray crystallographic methods, nuclear magnetic resonance (NMR) methods, and single-molecular fluorescence methods. ..
  24. Eliezer Masliah; Fiscal Year: 2014
    ..Thus, enhancing autophagy and lysosomal degradation of alpha-syn may represent a promising therapeutical strategy for the treatment not only for LBD but also for AD. ..
  25. Kejal Kantarci; Fiscal Year: 2015
    ..Finally, we will translate MRS and DTI markers to clinically valid measures of pathological severity. ..
  26. Robert A Rissman; Fiscal Year: 2015
    ..abstract_text> ..
  27. Alpha-Synuclein: A Drug Target for Parkinson's Disease
    Michael Lebowitz; Fiscal Year: 2001
    ..proposed commercial application: not available ..
  28. Eunsung Junn; Fiscal Year: 2015
    ..Therefore, learning what controls the amount of this protein will help devise new treatments of these diseases. This project will study a new mechanism that controls alpha-synuclein levels. ..
  29. Robert H Edwards; Fiscal Year: 2014
    ..abstract_text> ..
  30. Peter T Nelson; Fiscal Year: 2014
    ..The primary cel culture system will offer an experimental paradigm for testing novel methods of attenuating the dimorphic expression of miR-497 that drives alpha-SN expression. ..
  31. John Q Trojanowski; Fiscal Year: 2016
    ..M.-Y. Lee;Project IV: "Immune Therapy To Block PD Transmission In Mice": PL - J.Q. Trojanowski;Co-I - V.M.-Y. Lee and Kelvin Luk. ..
  32. Pamela J McLean; Fiscal Year: 2015
    ....
  33. Jianhua Zhang; Fiscal Year: 2014
    ..Our work will determine the function of the autophagy-lysosomal pathway in reducing a-syn level and toxicity, a strategy relevant to improving treatment of PD and other a-synucleinopathies. ..
  34. CNS MECHANISMS IN COCAINE-RELATED SUDDEN DEATH
    Deborah C Mash; Fiscal Year: 2012
    ..We have demonstrated that alpha synuclein, a protein implicated in neurodegenerative disorders, such as Parkinson's disease, may play a role in ..
  35. Habibeh Khoshbouei; Fiscal Year: 2014
    ....
  36. The Effects of Traumatic Brain Injury in Alpha Synuclein and Dopamine Regulation
    Samuel Shin; Fiscal Year: 2012
    ..Understanding this mechanism will help us develop therapeutic strategies to treat functional deficits after TBI and possible future development of neurodegenerative diseases. ..
  37. Pathological interactions of a-syn, mitochondria, and pesticides in PD models
    Michael K Lee; Fiscal Year: 2010
    ..Our finding will lead to better understanding of PD and new targets for therapeutic intervention. ..
  38. ORNIT FALEK; Fiscal Year: 2016
    ....
  39. Developing Diagnostic Nanobodies Against Aggregated TDP-43 Species
    Michael R Sierks; Fiscal Year: 2013
    ..Here we will develop and test similar reagents for detecting specific forms of TDP-43 that are present in FTD and ALS brain tissue. ..
  40. Parkinson's Disease Mouse Model with Mutant LRRK2
    Christopher A Ross; Fiscal Year: 2011
    ..Future studies of the role of kinase activity could clarify pathogenesis. Furthermore LRRK2 kinase may be an excellent therapeutic target, and mouse models would be valuable for preclinical therapeutic trials. ..
  41. INTERACTIONS BETWEEN ALPHA-SYNUCLEIN/METALS/PESTICIDES
    Donato Di Monte; Fiscal Year: 2003
    ....
  42. Michael R Sierks; Fiscal Year: 2014
    ..Here we will develop and test similar reagents for detecting specific forms of tau that are present in AD brain tissue. ..
  43. Jonathan Weare; Fiscal Year: 2016
    ....
  44. Molecular Regulation of Alpha-Synuclein Misfolding and Toxicity in Two Yeast Mode
    SHUBHIK DEBBURMAN; Fiscal Year: 2009
    ....
  45. Mitochondrial Proteins in Parkinson's Disease
    J Timothy Greenamyre; Fiscal Year: 2013
    ....
  46. Role of Nuclear Gangliosides in Neuronal Function
    Robert W Ledeen; Fiscal Year: 2012
    ..abstract_text> ..
  47. Post-translational Modifications of Proteins in Parkinson?s disease
    Jing Zhang; Fiscal Year: 2012
    ..Identification of these makers can increase therapeutic window for Parkinson's patients at risk for developing dementia that is associated with mortality, caregiver burden and risk for nursing home admission. ..
  48. RNA Targeted Screens of the Prion 5'UTR
    Jack T Rogers; Fiscal Year: 2010
    ..transfection based screen of an important RNA target, the 5'untranslated region of the Parkinson's alpha synuclein (ASYN) transcript...
  49. VIVEK UNNI; Fiscal Year: 2014
    ....
  50. Mark S Moehle; Fiscal Year: 2014
    ....
  51. Jonathan N Sachs; Fiscal Year: 2016
    ..e., restoring proper vesicle trafficking). ..
  52. Roles of alpha-synuclein in stroke induced brain damage
    Sic L Chan; Fiscal Year: 2010
    ..Our studies will provide new perspectives on the pathological role of a-synuclein in cerebral ischemia and potential cellular targets for blocking a-synuclein accumulation. ..
  53. GENETICS AND MOLECULAR BIOLOGY OF PARKINSONISM
    Dennis Dickson; Fiscal Year: 2009
    ..abstract_text> ..
  54. James Cleary; Fiscal Year: 2015
    ..abstract_text> ..
  55. Toxicants and innate immunity in models of Parkinson's disease
    Thomas J Montine; Fiscal Year: 2013
    ..abstract_text> ..
  56. Single-molecule fluorescence to characterize alpha synuclein transition to toxic
    ADAM TREXLER; Fiscal Year: 2011
    ..Parkinson's is characterized by the presence of Lewy bodies, intracellular plaques primarily composed of alpha synuclein. While large insoluble alpha synuclein aggregates are found in Lewy bodies, smaller soluble alpha synuclein ..
  57. LRRK2 and Parkinson's Disease Cell Biology
    Christopher A Ross; Fiscal Year: 2011
    ..These studies will help define the role of LRRK2 and its interacting proteins in cellular pathogenesis related to PD, and potentially identify targets for future therapeutic interventions. ..
  58. FREE RADICALS, PROTEIN AGGREGATES & PARKINSON'S DISEASE
    GARY PIELAK; Fiscal Year: 2001
    ..Site-specific variants of both proteins will used to locate the radicals in the primary structure. Mass spectrometry and amino acid analysis will be used to demonstrate crosslinking, and SDS PAGE will be used to assess aggregation. ..
  59. Anna E Rhoades; Fiscal Year: 2016
    ..Such understanding is critical to the long term goal of our research group to identify potential molecular targets for the development of therapeutics to treat or prevent Parkinson's disease. ..
  60. PD iPS Cell Line Consortium
    Ole Isacson; Fiscal Year: 2013
    ..Wszoiek that will provide necessary patient fibroblast lines, including GBA, FTD and additional LRRK2 and alpha synuclein mutations, along with a mRNA sequencing and expression laboratory...
  61. Structure and Mechanism of the Parkin Ubiquitin Ligase
    Brenda Schulman; Fiscal Year: 2003
    ..The PARK5 gene is thought to encode UCH-L1, a ubiquitin C terminal hydrolase. The PARK1 gene encodes alpha-synuclein, which is found along with ubiquitin in Lewy Bodies...
  62. ANTHONY ROBERT BRAUN; Fiscal Year: 2014
    ..Each of these aims will test our hypothesis that the intrinsic, natural curvature of alpha-S dictates its capacity to remodel and stabilize membranes, in particular those that are highly curved (like synaptic vesicles). ..
  63. Role of Protein-Lipid Bilayer Interactions in alpha-Syn*
    Anneta Razatos; Fiscal Year: 2005
    ..The AFM will also be used to observe the formation of alphaS aggregates on lipid bilayers. Ultimately, results from this study will be used to develop therapies that prevent alphaS aggregation. ..