Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson ’ s disease

  • Seol W
  • 19

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Parkinsons disease (PD) is the second most common neuro- degenerative disease, and 5-10% of the PD cases are genet- ically inherited as familial PD (FPD). LRRK2 (leucine-rich re- peat kinase 2) was first reported in 2004 as a gene correspond- ing to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein interaction motifs such as LRR (leucine-rich repeat) and WD40. Most pathogenic LRRK2 mutations are located in either the GTPase or kinase domain, implying important roles for the enzymatic activities in PD pathogenic mechanisms. In comparison to other PD causative genes such as parkin and PINK1, LRRK2 exhibits two important features. One is that LRRK2s mutations (especially the G2019S mutation) were observed in sporadic as well as familial PD patients. Another is that, among the various PD- causing genes, pathological characteristics observed in patients carrying LRRK2 mutations are the most similar to patients with sporadic PD. Because of these two observations, LRRK2 has been intensively investigated for its pathogenic mechanism (s) and as a target gene for PD therapeutics. In this review, the general biochemical and molecular features of LRRK2, the re- cent results of LRRK2 studies and LRRK2s therapeutic poten- tial as a PD target gene will be discussed.

Author-supplied keywords

  • 5 10
  • although most pd cases
  • bmbreports
  • cas
  • g2019s
  • genetics parkinson
  • gtpase
  • http
  • kinase
  • lrrk2
  • occur sporadically
  • org
  • parkinson
  • s disease

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Wongi Seol

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free