Exp Neurobiol.  2013 Jun;22(2):77-83. 10.5607/en.2013.22.2.77.

Alpha-Synuclein Expression in Patients with Parkinson's Disease: A Clinician's Perspective

• Kim HJ

• KMID: 1427105
• DOI: http://doi.org/10.5607/en.2013.22.2.77

Abstract

Although physiological function of alpha-synuclein is not yet clearly understood, accumulating evidence strongly suggests it plays a crucial role in the pathogenesis of Parkinson disease. Pathologically, alpha-synuclein is a major component of Lewy bodies, which is the pathological hallmark of Parkinson disease. Alpha-synuclein pathology is observed in the brainstem nuclei, including the dorsal motor nucleus of the vagus nerve, the locus ceruleus, and the substantia nigra in the early phase of Parkinson disease and it may 'spread' to cerebral cortical areas in the advanced Parkinson disease and appears to have a role in the cognitive decline in Parkinson disease. Recently, it is suggested that alpha-synuclein pathology in Parkinson disease starts in the olfactory bulb or enteric nervous system and then spreads to the brainstem. In accordance with this hypothesis, alpha-synuclein pathology has been found in gastric mucosa and colonic mucosa of patients with Parkinson disease. Genetically, SNCA mutations including point mutation and copy number variation are known to cause familial Parkinson disease, further supporting the assumption that alpha-synuclein plays a crucial role in Parkinson disease pathogenesis. In addition, recent GWAS studies consistently show that the SNPs in SNCA genes are associated with risk for sporadic Parkinson disease. It is also known that variations in the promoter region or 3'UTR of SNCA, which increases the expression of SNCA, are associated with the risk for Parkinson disease. Collectively, these findings suggest that further studies on alpha-synuclein will lead to the elucidation of the mechanism of and therapy for Parkinson disease.

Keyword

Parkinson disease; alpha-synuclein; neuropathology; genetics

MeSH Terms

3' Untranslated Regions
alpha-Synuclein
Brain Stem
Coat Protein Complex I
Colon
Enteric Nervous System
Gastric Mucosa
Humans
Lewy Bodies
Locus Coeruleus
Mucous Membrane
Olfactory Bulb
Parkinson Disease
Point Mutation
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Substantia Nigra
Vagus Nerve
3' Untranslated Regions
Coat Protein Complex I
alpha-Synuclein