Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review

Int J Mol Sci. 2022 Oct 3;23(19):11744. doi: 10.3390/ijms231911744.


Parkinson's disease is one of the most common neurodegenerative diseases affecting the ageing population, with a prevalence that has doubled over the last 30 years. As the mechanism of the disease is not fully elucidated, the current treatments are unable to effectively prevent neurodegeneration. Studies have found that mutations in Leucine-rich-repeat-kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). Moreover, aberrant (higher) LRRK2 kinase activity has an influence in idiopathic PD as well. Hence, the aim of this review is to categorize and synthesize current information related to LRRK2-linked PD and present the factors associated with LRRK2 that can be targeted therapeutically. A systematic review was conducted using the databases PubMed, Medline, SCOPUS, SAGE, and Cochrane (January 2016 to July 2021). Search terms included "Parkinson's disease", "mechanism", "LRRK2", and synonyms in various combinations. The search yielded a total of 988 abstracts for initial review, 80 of which met the inclusion criteria. Here, we emphasize molecular mechanisms revealed in recent in vivo and in vitro studies. By consolidating the recent updates in the field of LRRK2-linked PD, researchers can further evaluate targets for therapeutic application.

Keywords: LRRK2; Parkinson’s disease; mechanism.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Leucine / therapeutic use
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Mutation
  • Neurodegenerative Diseases* / metabolism
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / genetics


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