What have PINK1 and HtrA2 genes told us about the role of mitochondria in Parkinson's disease?
Parkinson's disease (PD) is a common, disabling, neurodegenerative disease. Our knowledge of the molecular events leading to PD is being greatly enhanced by the study of relatively rare familial form of the disease. Nevertheless, the pathways leading from the genetic mutations to nigral cell degeneration and the other features in PD remain poorly understood. The identification of PINK1, a mitochondrial putative protein kinase, has helped understand the pathophysiology of mitochondria and their potential role in PD. Mutations in PINK1 are associated with the PARK6 autosomal recessive, early-onset, PD-susceptibility locus. Point mutations in another mitochondrial protein, HtrA2, are a susceptibility factor for PD (PARK13 locus). We report here the results of investigations into the interactors and pathways of these two mitochondrial molecules (PINK1 and HtrA2) in a range of models and human PD tissue.
Plun-Favreau
Helene
H
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, UK. hpfavreau@googlemail.com
Gandhi
Sonia
S
Wood-Kaczmar
Alison
A
Deas
Emma
E
Yao
Zhi
Z
Wood
Nicholas W
NW
D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D000074923:High-Temperature Requirement A Serine Peptidase 2; D024101:Mitochondrial Proteins; D011494:Protein Kinases; D012697:Serine Endopeptidases; D000099202:PTEN-Induced Putative Kinase; C000615914:HTRA2 protein, human