The biology and pathobiology of LRRK2: Implications for Parkinson's disease
- 31 July 2008
- journal article
- review article
- Published by Elsevier BV in Parkinsonism & Related Disorders
- Vol. 14, S92-S98
- https://doi.org/10.1016/j.parkreldis.2008.04.010
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are an important cause of late-onset, familial and sporadic Parkinson's disease. LRRK2 is a large unique protein containing both GTPase and kinase enzymatic domains together with multiple protein-protein interaction domains. LRRK2 initially appears to function as a GTPase-regulated protein kinase. The majority of pathogenic mutations lead to enhanced kinase activity of LRRK2. Disease-associated mutations in LRRK2 also promote the formation of cytoplasmic inclusions and induce neuronal toxicity in cultured cells in a kinase-dependent manner. These and other important aspects of LRRK2 biology and pathophysiology are discussed in detail in this review.Keywords
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