Expanding insights of mitochondrial dysfunction in Parkinson's disease.
The quest to disentangle the aetiopathogenesis of Parkinson's disease has been heavily influenced by the genes associated with the disease. The alpha-synuclein-centric theory of protein aggregation with the adjunct of parkin-driven proteasome deregulation has, in recent years, been complemented by the discovery and increasing knowledge of the functions of DJ1, PINK1 and OMI/HTRA2, which are all associated with the mitochondria and have been implicated in cellular protection against oxidative damage. We critically review how these genes fit into and enhance our understanding of the role of mitochondrial dysfunction in Parkinson's disease, and consider how oxidative stress might be a potential unifying factor in the aetiopathogenesis of the disease.
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Patrick M
PM
Abou-Sleiman
Miratul M K
MM
Muqit
Nicholas W
NW
Wood
D000818:Animals; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D000074923:High-Temperature Requirement A Serine Peptidase 2; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D012697:Serine Endopeptidases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human; C000615914:HTRA2 protein, human