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Abstract <p>Leucine-rich repeat kinase 2 (LRRK2) belongs to the subfamily of tyrosine kinase-like kinases, the main function of which is to catalyze the transfer of γ-phosphate from ATP to the substrate in the cell due to the kinase domains. The exact functions of LRRK2 in the cell remain unknown. It has been shown that mutations in the <i>LRRK2</i> gene, which are the cause of the development of the most common autosomal dominant form of neurodegenerative disease, Parkinson’s disease (PD), mainly lead to a pathological increase in kinase activity. This review describes the structure of LRRK2 and the functional activity of LRRK2 kinase in the form of a monomer, dimer, and even a tetramer and describes the effect of mutations in the <i>LRRK2</i> gene on the structure and kinase activity of the LRRK2 enzyme. Understanding the structure and functions of LRRK2 opens up new prospects for using it as a target for PD therapy.</p>

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Parkinson’s Disease Associated with Mutations in the LRRK2 Gene: Approaches to Therapy

  • 期刊论文

  • 发表日期：

    2025年6月25日

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  • T. S. Usenko,
  • S. N. Pchelina

摘要

Abstract

Leucine-rich repeat kinase 2 (LRRK2) belongs to the subfamily of tyrosine kinase-like kinases, the main function of which is to catalyze the transfer of γ-phosphate from ATP to the substrate in the cell due to the kinase domains. The exact functions of LRRK2 in the cell remain unknown. It has been shown that mutations in the LRRK2 gene, which are the cause of the development of the most common autosomal dominant form of neurodegenerative disease, Parkinson’s disease (PD), mainly lead to a pathological increase in kinase activity. This review describes the structure of LRRK2 and the functional activity of LRRK2 kinase in the form of a monomer, dimer, and even a tetramer and describes the effect of mutations in the LRRK2 gene on the structure and kinase activity of the LRRK2 enzyme. Understanding the structure and functions of LRRK2 opens up new prospects for using it as a target for PD therapy.