TITLE:
Alpha-synuclein truncation and disease
AUTHORS:
Caroline M. Ritchie, Philip J. Thomas
KEYWORDS:
Alpha-Synuclein; Neurodegeneration; Parkinson’s Disease; Lewy Body; Proteasome; Truncation; Degradation; Aggregation; Protease
JOURNAL NAME:
Health,
Vol.4 No.11A,
November
29,
2012
ABSTRACT: Alpha-synuclein is the major component of Lewy bodies, insoluble protein aggregates, found in patients with Parkinson’s disease, diffuse Lewy body disease, and the Lewy body variant of Alzheimer’s disease. Alpha-synuclein has been found within Lewy bodies to contain many different modifications, including nitration, phosphorylation, ubiquitination, and truncation. C-terminally truncated forms of alpha-synuclein aggregate faster than the full-length protein in vitro, and are thus believed to play a role in Lewy body formation and disease progression. Pathological studies of post mortem brain tissue and the generation of transgenic mouse models further support a role of C-terminally truncated forms of alpha-synuclein in disease. Several enzymes, some of which function extracellularly, have been implicated in the production of these C-terminally truncated forms of alpha-synuclein. However, the enzymes responsible for alphasynuclein truncation in vivo have not yet been firmly established.