α-Synuclein and mitochondrial dysfunction in Parkinson's disease.
α-Synuclein (SNCA) is a substantive component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD). The discovery and subsequent derivation of its role in PD has led to a suprising but fruitful convergence of the fields of biochemistry and molecular genetics. In particular, the manipulation of the cell lines of a number of forms of familial PD has implicated SNCA in distinct and diverse biochemical pathways related to its pathogenesis. This current and rapidly evolving concept indicates PD is a disease in which interacting pathways of oxidative stress, mitochondrial dysfunction and impaired regulation of protein turnover interact to cause dopaminergic cell dysfunction and death. SNCA has a central role in these processes and manipulation of its expression, degradation and aggregation appear to be promising neuroprotective therapeutic targets.
Department of Clinical Neurosciences, UCL, Institute of Neurology, Royal Free Campus, Pond Street, London NW3 2QG, UK. s.mullin@nhs.net
Stephen
S
Mullin
Anthony
A
Schapira
D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051844:alpha-Synuclein / Q000235:genetics / Q000502:physiology*
D051844:alpha-Synuclein