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

Ann Clin Transl Neurol. 2023 Jun;10(6):850-864. doi: 10.1002/acn3.51776. Epub 2023 Apr 6.

Abstract

LRRK2 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.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Lewy Bodies / pathology
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

Grants and funding

This work was funded by Fonds de recherche du Quebec – Santé; Healthy Brains, Healthy Lives.