Strengths, Weaknesses, Opportunities, and Potential Threat Analysis of Targeting Leucine-Rich Repeat Kinase 2 for Parkinson's Disease Treatment: Status Quo and Quo Vadis

J Med Chem. 2025 Jul 10;68(13):13148-13168. doi: 10.1021/acs.jmedchem.5c00013. Epub 2025 Jun 30.

Abstract

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, and no curative treatments are currently available. Mutations in the LRRK2 gene, which encodes leucine-rich repeat kinase 2 (LRRK2), are among the most frequent genetic causes of both familial and sporadic PD cases. These pathogenic mutations enhance the kinase activity of LRRK2, and preclinical studies have indicated that inhibitors of LRRK2 kinase provide neuroprotection, making LRRK2 a promising therapeutic target for PD. In recent years, efforts to develop innovative therapies targeting LRRK2 have intensified, driving advancements in PD drug development. Here, we provide a comprehensive SWOT analysis of the strengths, weaknesses, opportunities, and threats of targeting LRRK2 for PD treatments.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / antagonists & inhibitors
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / metabolism
  • Mutation
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / pharmacology
  • Protein Kinase Inhibitors* / therapeutic use

Substances

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