Alpha-synuclein

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Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, where it is seen mainly in presynaptic terminals. It is predominantly expressed in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum. It is predominantly a neuronal protein, 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.

Alpha-synuclein is specifically upregulated in a discrete population of presynaptic terminals of the songbird brain during a period of song-acquisition-related synaptic rearrangement.

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.