Leucine rich repeat kinase 2 and dominantly inherited Parkinson disease

National Institute On Aging

Investigators

Linked publications & trials

Abstract

Our main aim in this project is to understand how mutations across many different domains of LRRK2 cause dominantly inherited Parkinsons disease. Our work in the past few years has focussed on the relationship between LRRK2, function of lysosomes and the accumulation of phosphorylated forms of RAB proteins at various membrane compartments of the cell. We have delineated the molecular machinery associated with activation of LRRK2 at damaged lysosomes and shown that the consequence of LRRK2 activity is to generate novel membrane-derived structures that are extended along microtubule tracks by interactions between phosphorylated RABS and various motor proteins. Ongoing work in the lab is focussed on mechanisms by which LRRK2 identifies damaged lysosomes, with specific candidates being validated.