The emerging role of LRRK2 in tauopathies

Clin Sci (Lond). 2022 Jul 15;136(13):1071-1079. doi: 10.1042/CS20220067.

Abstract

Parkinson's disease (PD) is conventionally described as an α-synuclein aggregation disorder, defined by Lewy bodies and neurites, and mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common autosomal dominant cause of PD. However, LRRK2 mutations may be associated with diverse pathologies in patients with Parkinson's syndrome including tau pathology resembling progressive supranuclear palsy (PSP). The recent discovery that variation at the LRRK2 locus is associated with the progression of PSP highlights the potential importance of LRRK2 in tauopathies. Here, we review the emerging evidence and discuss the potential impact of LRRK2 dysfunction on tau aggregation, lysosomal function, and endocytosis and exocytosis.

Keywords: LRRK2; Parkinson's disease; Progressive Supranuclear Palsy; Tau.

Publication types

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

MeSH terms

  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Mutation
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology
  • Tauopathies* / genetics
  • alpha-Synuclein / genetics

Substances

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