LRRK2 and Parkinson's disease: from genetics to targeted therapy

Abstract

AbstractLRRK2 variants are implicated in both familial and sporadic PD. LRRK2‐PD has a generally benign clinical presentation and variable pathology, with inconsistent presence of Lewy bodies and marked Alzheimer's disease pathology. The mechanisms underlying LRRK2‐PD are still unclear, but inflammation, vesicle trafficking, lysosomal homeostasis, and ciliogenesis have been suggested, among others. As novel therapies targeting LRRK2 are under development, understanding the role and function of LRRK2 in PD is becoming increasingly important. Here, we outline the epidemiological, pathophysiological, and clinical features of LRRK2‐PD, and discuss the arising therapeutic approaches targeting LRRK2 and possible future directions for research.