Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2

نویسندگان

  • Xianming Deng
  • Nicolas Dzamko
  • Alan Prescott
  • Paul Davies
  • Qingsong Liu
  • Qingkai Yang
  • Jiing-Dwan Lee
  • Matthew P. Patricelli
  • Tyzoon K. Nomanbhoy
  • Dario R. Alessi
  • Nathanael S. Gray
چکیده

Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. We employed a new, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor, LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910 and Ser935 and accumulation of LRRK2 within aggregate structures. LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson's disease.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2011