Alpha-synuclein
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Alpha-synuclein is a normal protein found in the brain. It is predominantly a presynaptic neuronal protein of unknown function, but can also be found in glial cells.
Recent evidence suggests that alpha-synuclein functions as a molecular chaperone in the formation of SNARE complexes.
Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC) is found in amyloid plaques in Alzheimer's disease.
In rare cases of familial forms of Parkinson's disease there is a mutation in the gene coding for alpha synuclein. Three point mutations have been identified thus far: A53T, A30P and E46K. In addition, triplication of the gene appears to be the cause of Parkinson's disease in another lineage.
Antibodies against alpha-synuclein have replaced antibodies against ubiquitin as the gold standard for immunostaining of Lewy bodies.
[edit] References
- Mihael H. Polymeropoulos et al.: Mutation in the α-Synuclein Gene Identified in Families with Parkinson’s Disease. In: Science 1997 June 27; 276: 2045-2047
- Manuela Neumann et al.: Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies. In: J Clin Invest. 2002 November 15; 110(10): 1429–1439
- Sandra Blakeslee: In Folding Proteins, Clues to Many Diseases. In: The New York Times, May 27 2002
