Journal
ACTA NEUROPATHOLOGICA
Volume 134, Issue 6, Pages 819-838Publisher
SPRINGER
DOI: 10.1007/s00401-017-1755-1
Keywords
Alpha-synuclein; Parkinson's; Oligomers; Aggregation; Detection-method
Categories
Funding
- Network of Centres of Excellence in Neurodegeneration (COEN)
- Parkinson's Disease Foundation [PDF-FBS-1638]
- Cure Parkinson's Trust [PDF-FBS-1638]
- Michael J Fox Foundation [PDF-FBS-1638]
- Monument Trust Discovery Award from Parkinson's UK
- MRC [MR/P007058/1] Funding Source: UKRI
- Medical Research Council [MR/P007058/1] Funding Source: researchfish
- Parkinson's UK [J-0901, J-1403, G-1003, H-1301] Funding Source: researchfish
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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.
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