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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Parkinson's disease and other alpha-synucleinopathies
1Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. mg@mrc-lmb.cam.ac.uk
Clinical Chemistry and Laboratory Medicine
|June 5, 2001
Summary
Parkinson's disease and related dementias are linked to alpha-synuclein protein aggregation. This study establishes alpha-synucleinopathies as a key class of neurodegenerative disease.
Area of Science:
- Neurodegenerative diseases
- Molecular biology
- Protein aggregation
Background:
- Parkinson's disease (PD) is a common movement disorder and the second leading neurodegenerative disease.
- Neuropathologically, PD involves nerve cell degeneration with Lewy bodies/neurites.
- Familial PD is linked to alpha-synuclein gene mutations, and PD lesions contain alpha-synuclein.
Purpose of the Study:
- To investigate the role of alpha-synuclein in neurodegenerative diseases.
- To establish a molecular link between Lewy body diseases and other neurodegenerative conditions.
- To classify alpha-synucleinopathies as a major group of neurodegenerative disorders.
Main Methods:
- Analysis of pathological lesions in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.
- Genetic analysis of familial Parkinson's disease.
- In vitro assembly of recombinant alpha-synuclein and related proteins.
Main Results:
- Filamentous lesions in PD, dementia with Lewy bodies, and multiple system atrophy are composed of alpha-synuclein.
- Alpha-synuclein gene mutations cause familial PD.
- Recombinant alpha-synuclein self-assembles into amyloid-like filaments, unlike beta- and gamma-synuclein.
Conclusions:
- Alpha-synuclein is the primary component of pathological inclusions in a range of neurodegenerative diseases.
- Alpha-synucleinopathies represent a significant class of neurodegenerative disorders.
- The findings provide a unifying molecular basis for these diseases.
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