Current Medical Science

, Volume 38, Issue 6, pp 1012–1017 | Cite as

LRRK2 G2019S Mutation Inhibits Degradation of α-Synuclein in an In Vitro Model of Parkinson’s Disease

  • Dan Hu
  • Jian-yi Niu
  • Jing Xiong
  • Shu-ke Nie
  • Fei Zeng
  • Zhao-hui ZhangEmail author


The G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of Parkinson’s disease (PD). However, the molecular mechanisms of LRRK2 mutation contributing to the onset and progression of PD have not been fully illustrated. We generated HEK293 cells stably transfected with α-synuclein and investigated the effect of LRRK2 G2019S mutation on the degradation of α-synuclein. The lysosomal activity was assessed by the protein degradation of glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A. It was found that α-synuclein was mainly degraded in lysosomes. LRRK2 G2019S inhibited the degradation of α-synuclein, and promoted its aggregation. LRRK2 G2019S also decreased the activities of lysosomal enzymes including cathepsin B and cathepsin L. Furthermore, the inhibitory effect of LRRK2 G2019S on lysosomal functions did not depend on its kinase activity. These findings indicated that the inhibitory effect of LRRK2 G2019S on α-synuclein degradation could underlie the pathogenesis of aberrant α-synuclein aggregation in PD with LRRK2 mutation.

Key words

α-synuclein leucine-rich repeat kinase 2 Parkinson’s disease lysosome 


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Copyright information

© Huazhong University of Science and Technology 2018

Authors and Affiliations

  • Dan Hu
    • 1
  • Jian-yi Niu
    • 2
  • Jing Xiong
    • 1
  • Shu-ke Nie
    • 1
  • Fei Zeng
    • 1
  • Zhao-hui Zhang
    • 1
    Email author
  1. 1.Department of NeurologyRenmin Hospital of Wuhan UniversityWuhanChina
  2. 2.Department of Neurology, Yidu Central HospitalWeifang Medical CollegeWeifangChina

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