Alpha-synuclein oligomers: a new hope
TLDR
The advances in understanding of the role of alpha-synuclein in Parkinson’s disease that may be brought about by the specific and sensitive detection of distinct oligomeric species in post-mortem patient brain are discussed.Abstract:
Alpha-synuclein is a protein implicated in Parkinson’s disease and thought to be one of the main pathological drivers in the disease, although it remains unclear how this protein elicits its neurotoxic effects. Recent findings indicate that the assembly of toxic oligomeric species of alpha-synuclein may be one of the key processes for the pathology and spread of the disease. The absence of a sensitive in situ detection method has hindered the study of these oligomeric species and the role they play in the human brain until recently. In this review, we assess the evidence for the toxicity and prion-like activity of oligomeric forms of alpha-synuclein and discuss the advances in our understanding of the role of alpha-synuclein in Parkinson’s disease that may be brought about by the specific and sensitive detection of distinct oligomeric species in post-mortem patient brain. Finally, we discuss current approaches being taken to therapeutically target alpha-synuclein oligomers and their implications.read more
Citations
More filters
Journal ArticleDOI
Selective neuronal vulnerability in Parkinson disease.
TL;DR: The evidence for and against the spreading LP model are discussed, as well as evidence that cell-autonomous factors govern both α-syn pathology and neuronal death.
Journal ArticleDOI
Dementia with Lewy bodies: an update and outlook
Tiago F. Outeiro,Tiago F. Outeiro,Tiago F. Outeiro,David J. Koss,Daniel Erskine,Lauren Walker,Marzena Kurzawa-Akanbi,David J. Burn,Paul C. Donaghy,Christopher Morris,John-Paul Taylor,Alan J. Thomas,Johannes Attems,Ian G. McKeith +13 more
TL;DR: Basic concepts and definitions of dementia with Lewy bodies are presented, based on the current understanding, that should guide the community to address open questions that will lead to improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies.
Journal ArticleDOI
Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force.
TL;DR: The authors reviewed similarities and differences among four main proteins, α-synuclein, FUS, tau, and TDP-43, which are found aggregated in different diseases and were independently shown to phase separate.
Journal ArticleDOI
Targeting Alpha-Synuclein as a Therapy for Parkinson's Disease.
TL;DR: Current advances in therapeutic efforts for PD that aim to produce a disease-modifying therapy by targeting the spread, production, aggregation, and degradation of alpha-synuclein are reviewed.
Journal ArticleDOI
Modeling Parkinson's Disease With the Alpha-Synuclein Protein
Mónica Gómez-Benito,Noelia Granado,Noelia Granado,Patricia García-Sanz,Patricia García-Sanz,Anne Michel,Mireille Dumoulin,Rosario Moratalla,Rosario Moratalla +8 more
TL;DR: It is shown that injection of α-Syn PFFs and overexpression ofα-Syn mediated by rAAV lead to a different pattern of PD pathology in rodents, suggesting that there is an inter-neuronal transmission of the α-synuclein pathology.
References
More filters
Journal ArticleDOI
Staging of brain pathology related to sporadic Parkinson’s disease
TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
Journal ArticleDOI
Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis
Rakez Kayed,Elizabeth Head,Jennifer L. Thompson,Theresa M. McIntire,Saskia Milton,Carl W. Cotman,Charles G. Glabe +6 more
TL;DR: It is shown that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomer regardless of sequence, suggesting they share a common mechanism of toxicity.
Journal ArticleDOI
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more
TL;DR: In this article, the α-synuclein was identified as the major component of Lewy bodies, the pathological hallmark of Parkinson's disease, and of glial cell cytoplasmic inclusions.
Related Papers (5)
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more