Leucine-rich repeat kinase 2 inhibitor as Parkinson’s disease novel therapeutics: Research advances / 国际药学研究杂志

ABSTRACT

Parkinson’s disease PD is a common disease caused by multiple factors and characterized by pathological degeneration in the dopaminergic neural system. Based on its pathogenic factors, PD can be divided into several subtypes, so it is essential to develop therapeutic agents based on the main pathogenic factor of each subtype of PD. Recently it is confirmed that the mutation of leucine- rich repeat kinase 2 LRRK2 gene leads to increased activity of the LRRK2 notably, and then causes neurodegeneration. Thus developing LRRK2 inhibitors to modulate the kinase activity will be a novel therapy for the PD subtype which is caused by LRRK2 gene mutation. LRRK2, either a kinase or a GTPase, has two drug binding sites. Therefore, two types of LRRK2 inhibitors are being studied, one is the kinase inhibitor and the other is GTPase inhibitor. This paper summarizes the recent progress in the discovery and development of LRRK2 inhibitors.