LRRK2
MIM.609007 12q12
Definition: Leucine-rich repeat kinase 2 (LRRK2) is a cytosolic kinase.
Pathology
germline mutations in autosomal dominant Parkinson disease
Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) were discovered in late-onset parkinsonism, the phenotype of which can be clinically and pathologically indistinguishable from Parkinson disease.
In some kindreds with LRRK2-associated disease, pathologically distinct forms of parkinsonism, including nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary tangles, were discovered.
Mutations in leucine-rich repeat kinase 2 (LRRK2), a cytosolic kinase, are dominant and have the opposite effect of causing neuronal damage. The mechanism(s) involved are uncertain at this time because LRRK2 is a large and complex molecule with several domains.
Increased kinase activity accounts for the action of at least some of the mutations, suggesting that hyperactive or misregulated kinase activity may lead to the damaging effects of LRRK2 in neurons. (MIM.607060)
See also
8 mutated Parkinson disease genes known (2008)
| SNCA | PARK2 | UCHL1 | PINK1 | DJ1 | LRRK2 | ATP13A2 | HTRA2 |
References
Taylor JP, Mata IF, Farrer MJ. LRRK2: a common pathway for parkinsonism, pathogenesis and prevention? Trends Mol Med. 2006 Feb;12(2):76-82. PMID: 16406842
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