Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations

[1]  R. Postuma,et al.  Parkinson risk in idiopathic REM sleep behavior disorder , 2015, Neurology.

[2]  G. Wenning,et al.  Multiple-system atrophy. , 2015, The New England journal of medicine.

[3]  A. Recasens,et al.  Alpha-synuclein spreading in Parkinson’s disease , 2014, Front. Neuroanat..

[4]  A. Paetau,et al.  A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology , 2014, Neurobiology of Aging.

[5]  E. Bézard,et al.  Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives , 2014, The Lancet.

[6]  C. Richie,et al.  The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse , 2014, Neurobiology of Disease.

[7]  E. Masliah,et al.  Overexpression of the calpain-specific inhibitor calpastatin reduces human alpha-Synuclein processing, aggregation and synaptic impairment in [A30P]αSyn transgenic mice. , 2014, Human molecular genetics.

[8]  Thomas G. Beach,et al.  Quantitative Measurement of Intact Alpha-Synuclein Proteoforms from Post-Mortem Control and Parkinson's Disease Brain Tissue by Intact Protein Mass Spectrometry , 2014, Scientific Reports.

[9]  E. Bézard,et al.  Multiple system atrophy: A prototypical synucleinopathy for disease-modifying therapeutic strategies , 2014, Neurobiology of Disease.

[10]  Chuong B. Do,et al.  Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease , 2014, Nature Genetics.

[11]  J. Trojanowski,et al.  α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration , 2014, Cell reports.

[12]  R. Barker,et al.  Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial , 2014, The Lancet.

[13]  K. Bötzel,et al.  The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset , 2014, Acta Neuropathologica.

[14]  Ye Han,et al.  Targeting alpha-synuclein with a microRNA-embedded silencing vector in the rat substantia nigra: Positive and negative effects , 2014, Brain Research.

[15]  E. Bézard,et al.  Lewy body extracts from Parkinson disease brains trigger α‐synuclein pathology and neurodegeneration in mice and monkeys , 2014, Annals of neurology.

[16]  E. Masliah,et al.  Next-generation active immunization approach for synucleinopathies: implications for Parkinson’s disease clinical trials , 2014, Acta Neuropathologica.

[17]  B. Giasson,et al.  Evidence of Native α-Synuclein Conformers in the Human Brain* , 2014, The Journal of Biological Chemistry.

[18]  Nick C Fox,et al.  Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. , 2014, The New England journal of medicine.

[19]  E. Siemers,et al.  Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. , 2014, The New England journal of medicine.

[20]  E. Schon,et al.  α-Synuclein Is Localized to Mitochondria-Associated ER Membranes , 2014, The Journal of Neuroscience.

[21]  B. Meier,et al.  Structural and functional characterization of two alpha-synuclein strains , 2013, Nature Communications.

[22]  R. Edwards,et al.  The Function of α-Synuclein , 2013, Neuron.

[23]  P. Aebischer,et al.  Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo , 2013, Proceedings of the National Academy of Sciences.

[24]  M. Colombo,et al.  Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms , 2013, Front. Cell. Infect. Microbiol..

[25]  Maria Xilouri,et al.  Boosting chaperone-mediated autophagy in vivo mitigates α-synuclein-induced neurodegeneration. , 2013, Brain : a journal of neurology.

[26]  C. Hetz,et al.  Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons , 2013, Autophagy.

[27]  M. Farrer,et al.  Alpha‐synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[28]  A. Rana,et al.  Alpha-Synuclein Induces Lysosomal Rupture and Cathepsin Dependent Reactive Oxygen Species Following Endocytosis , 2013, PloS one.

[29]  Anders Björklund,et al.  TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity , 2013, Proceedings of the National Academy of Sciences.

[30]  P. Tavan,et al.  Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease , 2013, Acta Neuropathologica.

[31]  Ronald Melki,et al.  G51D α‐synuclein mutation causes a novel Parkinsonian–pyramidal syndrome , 2013, Annals of neurology.

[32]  K. Brunden,et al.  Lewy Body-like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy*♦ , 2013, The Journal of Biological Chemistry.

[33]  Christos Proukakis,et al.  A novel α-synuclein missense mutation in Parkinson disease , 2013, Neurology.

[34]  E. Masliah,et al.  Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia , 2013, Nature Communications.

[35]  Nam Ki Lee,et al.  Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking , 2013, Proceedings of the National Academy of Sciences.

[36]  E. Bézard,et al.  Animal models of Parkinson's disease: Limits and relevance to neuroprotection studies , 2013, Movement disorders : official journal of the Movement Disorder Society.

[37]  H. Braak,et al.  100 years of Lewy pathology , 2013, Nature Reviews Neurology.

[38]  E. Masliah,et al.  The many faces of α-synuclein: from structure and toxicity to therapeutic target , 2012, Nature Reviews Neuroscience.

[39]  J. Trojanowski,et al.  Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice , 2012, Science.

[40]  E. Masliah,et al.  Antibody-Aided Clearance of Extracellular α-Synuclein Prevents Cell-to-Cell Aggregate Transmission , 2012, The Journal of Neuroscience.

[41]  V. Baekelandt,et al.  A prolyl oligopeptidase inhibitor, KYP‐2047, reduces α‐synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease , 2012, British journal of pharmacology.

[42]  Christopher M. Dobson,et al.  Direct Observation of the Interconversion of Normal and Toxic Forms of α-Synuclein , 2012, Cell.

[43]  M. Ivanova,et al.  A Novel “Molecular Tweezer” Inhibitor of α-Synuclein Neurotoxicity in Vitro and in Vivo , 2012, Neurotherapeutics.

[44]  Bernard Schneider,et al.  α-Synuclein in Central Nervous System and from Erythrocytes, Mammalian Cells, and Escherichia coli Exists Predominantly as Disordered Monomer* , 2012, The Journal of Biological Chemistry.

[45]  Jean-Christophe Rochet,et al.  Molecular insights into Parkinson's disease. , 2012, Progress in molecular biology and translational science.

[46]  S. Koyama,et al.  Authentically Phosphorylated α-Synuclein at Ser129 Accelerates Neurodegeneration in a Rat Model of Familial Parkinson's Disease , 2011, The Journal of Neuroscience.

[47]  Wei Wang,et al.  A soluble α-synuclein construct forms a dynamic tetramer , 2011, Proceedings of the National Academy of Sciences.

[48]  B. Hyman,et al.  Distinct Roles In Vivo for the Ubiquitin–Proteasome System and the Autophagy–Lysosomal Pathway in the Degradation of α-Synuclein , 2011, The Journal of Neuroscience.

[49]  J. Trojanowski,et al.  Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets. , 2011, Cold Spring Harbor perspectives in medicine.

[50]  D. Selkoe,et al.  α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation , 2011, Nature.

[51]  Marta Martínez-Vicente,et al.  Fighting neurodegeneration with rapamycin: mechanistic insights , 2011, Nature Reviews Neuroscience.

[52]  J. Trojanowski,et al.  α-Syn Suppression Reverses Synaptic and Memory Defects in a Mouse Model of Dementia with Lewy Bodies , 2011, The Journal of Neuroscience.

[53]  K. Bankiewicz,et al.  An alpha-synuclein AAV gene silencing vector ameliorates a behavioral deficit in a rat model of Parkinson's disease, but displays toxicity in dopamine neurons , 2011, Brain Research.

[54]  E. Masliah,et al.  Enhanced Phosphatase Activity Attenuates α-Synucleinopathy in a Mouse Model , 2011, The Journal of Neuroscience.

[55]  Paola Piccini,et al.  Priorities in Parkinson's disease research , 2011, Nature Reviews Drug Discovery.

[56]  E. Masliah,et al.  Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease , 2011, PloS one.

[57]  Fred H. Gage,et al.  In vivo demonstration that α-synuclein oligomers are toxic , 2011, Proceedings of the National Academy of Sciences.

[58]  M. Spillantini,et al.  Induction of the unfolded protein response by α‐synuclein in experimental models of Parkinson’s disease , 2011, Journal of neurochemistry.

[59]  V. Subramaniam,et al.  Membrane Permeabilization by Oligomeric α-Synuclein: In Search of the Mechanism , 2010, PloS one.

[60]  J. Jankovic,et al.  Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial , 2010, The Lancet Neurology.

[61]  Steve D. M. Brown,et al.  α-Synuclein impairs macroautophagy: implications for Parkinson’s disease , 2010, The Journal of cell biology.

[62]  M. Vila,et al.  Pathogenic Lysosomal Depletion in Parkinson's Disease , 2010, The Journal of Neuroscience.

[63]  A. Cuervo,et al.  Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation , 2010, Neurobiology of Disease.

[64]  J. Henderson,et al.  α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra , 2010, PloS one.

[65]  Fabia Febbraro,et al.  Co‐expression of C‐terminal truncated alpha‐synuclein enhances full‐length alpha‐synuclein‐induced pathology , 2010, The European journal of neuroscience.

[66]  R. Mandel,et al.  In Vivo RNAi-Mediated α-Synuclein Silencing Induces Nigrostriatal Degeneration. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[67]  Min Jae Lee,et al.  Enhancement of Proteasome Activity by a Small-Molecule Inhibitor of Usp14 , 2010, Nature.

[68]  R. Krüger,et al.  First appraisal of brain pathology owing to A30P mutant alpha‐synuclein , 2010, Annals of neurology.

[69]  D. Ehrnhoefer,et al.  EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity , 2010, Proceedings of the National Academy of Sciences.

[70]  Nick C Fox,et al.  11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study , 2010, The Lancet Neurology.

[71]  Lloyd A Greene,et al.  Rapamycin Protects against Neuron Death in In Vitro andIn Vivo Models of Parkinson's Disease , 2010, The Journal of Neuroscience.

[72]  E. Masliah,et al.  Beclin 1 Gene Transfer Activates Autophagy and Ameliorates the Neurodegenerative Pathology in α-Synuclein Models of Parkinson's and Lewy Body Diseases , 2009, The Journal of Neuroscience.

[73]  H. Jäckle,et al.  Pre‐fibrillar α‐synuclein variants with impaired β‐structure increase neurotoxicity in Parkinson's disease models , 2009, The EMBO journal.

[74]  C. Warren Olanow,et al.  Alterations in lysosomal and proteasomal markers in Parkinson's disease: Relationship to alpha-synuclein inclusions , 2009, Neurobiology of Disease.

[75]  S. Przedborski,et al.  Intrabody and Parkinson's disease. , 2009, Biochimica et biophysica acta.

[76]  David Park,et al.  Abberant α-Synuclein Confers Toxicity to Neurons in Part through Inhibition of Chaperone-Mediated Autophagy , 2009, PloS one.

[77]  E. Hirsch,et al.  Neuroinflammation in Parkinson's disease: a target for neuroprotection? , 2009, The Lancet Neurology.

[78]  E. Hirsch,et al.  Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. , 2008, The Journal of clinical investigation.

[79]  S. Lindquist,et al.  Hsp104 antagonizes alpha-synuclein aggregation and reduces dopaminergic degeneration in a rat model of Parkinson disease. , 2008, The Journal of clinical investigation.

[80]  P. Lansbury,et al.  Phosphorylation at Ser-129 but Not the Phosphomimics S129E/D Inhibits the Fibrillation of α-Synuclein* , 2008, Journal of Biological Chemistry.

[81]  D. Berg,et al.  Genetic variability in the SNCA gene influences α‐synuclein levels in the blood and brain , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[82]  R. Hauser,et al.  Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease , 2008, Nature Medicine.

[83]  Elisabet Englund,et al.  Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation , 2008, Nature Medicine.

[84]  Alain Dagher,et al.  Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years , 2008, Nature Medicine.

[85]  J. Jankovic Parkinson’s disease: clinical features and diagnosis , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[86]  Peter T Lansbury,et al.  Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. , 2008, The Journal of clinical investigation.

[87]  H. Gendelman,et al.  Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons , 2008, PloS one.

[88]  Armin Giese,et al.  Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding , 2007, The Journal of Neuroscience.

[89]  M. Feany,et al.  Aggregated α-Synuclein Mediates Dopaminergic Neurotoxicity In Vivo , 2007, The Journal of Neuroscience.

[90]  D. Rubinsztein,et al.  Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein* , 2007, Journal of Biological Chemistry.

[91]  R. Barbour,et al.  Phosphorylation of Ser-129 Is the Dominant Pathological Modification of α-Synuclein in Familial and Sporadic Lewy Body Disease* , 2006, Journal of Biological Chemistry.

[92]  M. Mattson,et al.  Ageing and neuronal vulnerability , 2006, Nature Reviews Neuroscience.

[93]  Hai Lin,et al.  Amyloid ion channels: a common structural link for protein-misfolding disease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[94]  M. Feany,et al.  α-Synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease , 2005, Nature Neuroscience.

[95]  Philippe Amouyel,et al.  α-synuclein locus duplication as a cause of familial Parkinson's disease , 2004, The Lancet.

[96]  Peter T. Lansbury,et al.  Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy , 2004, Science.

[97]  Jochen Klucken,et al.  Hsp70 Reduces α-Synuclein Aggregation and Toxicity* , 2004, Journal of Biological Chemistry.

[98]  Alexxai V. Kravitz,et al.  Fibrillization of α-synuclein and tau in familial Parkinson's disease caused by the A53T α-synuclein mutation , 2004, Experimental Neurology.

[99]  Takeshi Iwatsubo,et al.  Aggresomes Formed by α-Synuclein and Synphilin-1 Are Cytoprotective* , 2004, Journal of Biological Chemistry.

[100]  J. Hoenicka,et al.  The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia , 2004, Annals of neurology.

[101]  Janel O. Johnson,et al.  α-Synuclein Locus Triplication Causes Parkinson's Disease , 2003, Science.

[102]  B. Giasson,et al.  Effects of Oxidative and Nitrative Challenges on α-Synuclein Fibrillogenesis Involve Distinct Mechanisms of Protein Modifications* , 2003, Journal of Biological Chemistry.

[103]  Jeremy N. Skepper,et al.  α-Synuclein Is Degraded by Both Autophagy and the Proteasome* , 2003, Journal of Biological Chemistry.

[104]  E. Bézard Neuroprotection for Parkinson's disease: a call for clinically riven experimental design , 2003, The Lancet Neurology.

[105]  V. Uversky,et al.  Nitration inhibits fibrillation of human α‐synuclein in vitro by formation of soluble oligomers , 2003 .

[106]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[107]  P. Auluck,et al.  Pharmacological prevention of Parkinson disease in Drosophila , 2002, Nature Medicine.

[108]  P. Lansbury,et al.  Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism. , 2002, Biochemistry.

[109]  E. Masliah,et al.  α-Synuclein is phosphorylated in synucleinopathy lesions , 2002, Nature Cell Biology.

[110]  John Q. Trojanowski,et al.  Chaperone Suppression of α-Synuclein Toxicity in a Drosophila Model for Parkinson's Disease , 2001, Science.

[111]  Peter T. Lansbury,et al.  Kinetic Stabilization of the α-Synuclein Protofibril by a Dopamine-α-Synuclein Adduct , 2001, Science.

[112]  J Q Trojanowski,et al.  A Hydrophobic Stretch of 12 Amino Acid Residues in the Middle of α-Synuclein Is Essential for Filament Assembly* , 2001, The Journal of Biological Chemistry.

[113]  J. Trojanowski,et al.  Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. , 2000, Science.

[114]  P. Lansbury,et al.  Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[115]  L. Meijer,et al.  Constitutive Phosphorylation of the Parkinson's Disease Associated α-Synuclein* , 2000, The Journal of Biological Chemistry.

[116]  T. Chase,et al.  Degradation of α-Synuclein by Proteasome* , 1999, The Journal of Biological Chemistry.

[117]  Peter T. Lansbury,et al.  Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease , 1998, Nature Medicine.

[118]  Olaf Riess,et al.  AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease , 1998, Nature Genetics.

[119]  M. L. Schmidt,et al.  α-Synuclein in Lewy bodies , 1997, Nature.

[120]  Robert L. Nussbaum,et al.  Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease , 1997 .

[121]  P. Lansbury,et al.  NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. , 1996, Biochemistry.

[122]  Akihiko Iwai,et al.  The precursor protein of non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system , 1995, Neuron.

[123]  E. Masliah,et al.  Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.