LRRK2 Parkinson's disease: from animal models to cellular mechanisms

Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) play a major role in the development of Parkinson's disease. The most frequently defined mutations of LRRK2 are located in the central catalytic region of the LRRK2 protein, suggesting that dysregulations of its enzymatic activities contribute to PD pathogenesis. Herein, we review recent progress in research concerning how LRRK2 mutations affect cellular pathways and lead to neuronal degeneration. We also summarize recent evidence revealing the endogenous function of LRRK2 protein within cells. These concepts can be used to further understand disease pathophysiology and serve as a platform to develop therapeutic strategies for the treatment of Parkinson's disease.