Monday 21 April 2008
The PINK1 gene encodes a mitochondrially located serine/threonine kinase, the mitochondrial kinase PTEN (phosphatase and tensin homolog)-induced kinase 1 (PINK1).
germline mutations in early-onset autosomal recessive Parkinson disease locus 6 (PARK6) (MIM.605909)
variants in susceptibility to Parkinson disease
Although patients with PARK6 were originally found to have homozygous mutations in the PINK1 gene, a subset of patients have been reported with heterozygous mutations in the PINK1 gene, suggesting that heterozygous mutations may also contribute to disease development.
Mutations in the mitochondrial kinase PTEN (phosphatase and tensin homolog)-induced kinase 1 (PINK1) are loss-of-function mutations in a normally neuroprotective protein.
Loss-of-function mutations in model organisms have variable effects, from dramatic muscle and spermatid defects in Drosophila to more subtle neurophysiological abnormalities in mice.
Several lines of evidence relate these to the action of a second gene for familial PD, parkin, an E3 ubiquitin ligase shown recently to have effects on Akt signaling.
AKT/PIP3 signaling pathway
8 mutated Parkinson genes known (2008)
HtrA2 and Parkinson’s disease: think PINK? Emad S. Alnemri. Nature Cell Biology 9, 1227 - 1229 (2007)
Cookson MR, Dauer W, Dawson T, Fon EA, Guo M, Shen J. The roles of kinases in familial Parkinson’s disease. J Neurosci. 2007 Oct 31;27(44):11865-8. PMID: #17978026#