An Update on the Interplay between LRRK2, Rab GTPases and Parkinson's Disease.

Tadayuki Komori, Tomoki Kuwahara
Author Information
  1. Tadayuki Komori: Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ORCID
  2. Tomoki Kuwahara: Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. ORCID

Abstract

Over the last decades, research on the pathobiology of neurodegenerative diseases has greatly evolved, revealing potential targets and mechanisms linked to their pathogenesis. Parkinson's disease (PD) is no exception, and recent studies point to the involvement of endolysosomal defects in PD. The endolysosomal system, which tightly controls a flow of endocytosed vesicles targeted either for degradation or recycling, is regulated by a number of Rab GTPases. Their associations with leucine-rich repeat kinase 2 (LRRK2), a major causative and risk protein of PD, has also been one of the hot topics in the field. Understanding their interactions and functions is critical for unraveling their contribution to PD pathogenesis. In this review, we summarize recent studies on LRRK2 and Rab GTPases and attempt to provide more insight into the interaction of LRRK2 with each Rab and its relationship to PD.

Keywords

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Grants

  1. 22H02949/Japan Society for the Promotion of Science
  2. 22H04638/Japan Society for the Promotion of Science

MeSH Term

Humans
Parkinson Disease
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
rab GTP-Binding Proteins
Endosomes
Endocytosis
Mutation

Chemicals

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
rab GTP-Binding Proteins
LRRK2 protein, human

Word Cloud

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