Expert Reviews in Molecular Medicine

Review Article

Role of LRRK2 kinase dysfunction in Parkinson disease

Azad Kumara1 and Mark R. Cooksona1 c1

a1 Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.


Parkinson disease is a common and usually sporadic neurodegenerative disorder. However, a subset of cases are inherited and, of these, mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of disease. Here, we will discuss recent progress in understanding how LRRK2 mutations lead to disease and how this might have therapeutic implications. The effect of mutations on LRRK2 enzyme function provides clues as to which functions of the protein are important to disease. Recent work has focused on the kinase and GTP-binding domains of LRRK2, and it is assumed that these will be therapeutically important, although there is a substantial amount of work to be done to address this hypothesis.

(Online publication June 13 2011)