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LRRK2 in Parkinson's disease: function in cells and neurodegeneration.

Publication ,  Journal Article
Webber, PJ; West, AB
Published in: FEBS J
November 2009

The detailed characterization of the function of leucine-rich repeat kinase 2 (LRRK2) may provide insight into the molecular basis of neurodegeneration in Parkinson's disease (PD) because mutations in LRRK2 cause a phenotype with strong overlap to typical late-onset disease and LRRK2 mutations are responsible for significant proportions of PD in some populations. The complexity of large multidomain protein kinases such as LRRK2 challenges traditional functional approaches, although initial studies have successfully defined the basic mechanisms of enzyme activity with respect to the putative effects of pathogenic mutations on kinase activity. The role of LRRK2 in cells remains elusive, with potential function in mitogen-activated protein kinase pathways, protein translation control, programmed cell death pathways and activity in cytoskeleton dynamics. The initial focus on LRRK2-kinase-dependent phenomena places emphasis on the discovery of LRRK2 kinase substrates, although candidate substrates are so far confined to in vitro assays. Here, hypothetical mechanisms for LRRK2-mediated cell death and kinase activation are proposed. As a promising target for neuroprotection strategies in PD, in vitro and in vivo models that accurately demonstrate LRRK2's function relevant to neurodegeneration will aide in the identification of molecules with the highest chance of success in the clinic.

Duke Scholars

Published In

FEBS J

DOI

EISSN

1742-4658

Publication Date

November 2009

Volume

276

Issue

22

Start / End Page

6436 / 6444

Location

England

Related Subject Headings

  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Parkinson Disease
  • Mutation
  • Models, Biological
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Humans
  • Cell Death
  • Biochemistry & Molecular Biology
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Webber, P. J., & West, A. B. (2009). LRRK2 in Parkinson's disease: function in cells and neurodegeneration. FEBS J, 276(22), 6436–6444. https://doi.org/10.1111/j.1742-4658.2009.07342.x
Webber, Philip J., and Andrew B. West. “LRRK2 in Parkinson's disease: function in cells and neurodegeneration.FEBS J 276, no. 22 (November 2009): 6436–44. https://doi.org/10.1111/j.1742-4658.2009.07342.x.
Webber PJ, West AB. LRRK2 in Parkinson's disease: function in cells and neurodegeneration. FEBS J. 2009 Nov;276(22):6436–44.
Webber, Philip J., and Andrew B. West. “LRRK2 in Parkinson's disease: function in cells and neurodegeneration.FEBS J, vol. 276, no. 22, Nov. 2009, pp. 6436–44. Pubmed, doi:10.1111/j.1742-4658.2009.07342.x.
Webber PJ, West AB. LRRK2 in Parkinson's disease: function in cells and neurodegeneration. FEBS J. 2009 Nov;276(22):6436–6444.
Journal cover image

Published In

FEBS J

DOI

EISSN

1742-4658

Publication Date

November 2009

Volume

276

Issue

22

Start / End Page

6436 / 6444

Location

England

Related Subject Headings

  • Signal Transduction
  • Protein Serine-Threonine Kinases
  • Parkinson Disease
  • Mutation
  • Models, Biological
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Humans
  • Cell Death
  • Biochemistry & Molecular Biology
  • Animals