Parkin (ligase)
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For other uses, see Parkin (disambiguation).
Parkin is an E3 ligase in the ubiquitin-proteasome system. Many mutations in parkin have been associated with a familial form of Parkinson's disease termed autosomal recessive juvenile parkinsonism. How loss of function of parkin leads to dopaminergic cell death in this disease is unclear. The prevailing hypothesis is that parkin helps degrade one or more proteins toxic to dopaminergic neurons. Putative substrates of parkin include synphilin-1, CDC-rel1, CDC-rel2, cyclinE, p38 tRNA synthase, Pael-R, synaptotagmin XI, synphilin-1, sp22 and parkin itself. See also Ubiquitin ligase.
[edit] Parkinson's disease
PARK2 (OMIM *602544) is the parkin gene that may cause a form of autosomal recessive juvenile Parkinson disease (OMIM 600116) due to a mutation in the parkin protein. This form of genetic mutation may be one of the most common known genetic causes of early-onset Parkinson disease. In one study of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous mutations. [1] Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40). [2]
Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.
[edit] References
- ^ Poorkaj P et al. (2004). Parkin mutation analysis in clinic patients with early-onset Parkinson's disease. American Journal of Medical Genetics Part A 129A (1): 44–50.
- ^ Lohmann E, et al. (2003). How much phenotypic variation can be attributed to parkin genotype?. Annals of Neurology 54 (2): 176–185.
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