Mitochondrial alterations in Parkinson's disease: new clues.
Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease.
Vila
Miquel
M
Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain. mvila@ir.vhebron.net
Ramonet
David
D
Perier
Celine
C
D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D004272:DNA, Mitochondrial; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein