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Cell Death Differ. 2016 Mar;23(3):542-52. doi: 10.1038/cdd.2015.135. Epub 2015 Oct 30.

c-Abl-p38α signaling plays an important role in MPTP-induced neuronal death.

Wu R1,2, Chen H1,3, Ma J1,2, He Q1,2, Huang Q4, Liu Q5, Li M4, Yuan Z1,2,3.

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State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100069, China.
Department of Pharmacology and the Proteomics Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031, China.


Oxidative stress is a major cause of sporadic Parkinson's disease (PD). Here, we demonstrated that c-Abl plays an important role in oxidative stress-induced neuronal cell death. C-Abl, a nonreceptor tyrosine kinase, was activated in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced acute PD model. Conditional knockout of c-Abl in neurons or treatment of mice with STI571, a c-Abl family kinase inhibitor, reduced the loss of dopaminergic neurons and ameliorated the locomotive defects induced by short-term MPTP treatment. By combining the SILAC (stable isotope labeling with amino acids in cell culture) technique with other biochemical methods, we identified p38α as a major substrate of c-Abl both in vitro and in vivo and c-Abl-mediated phosphorylation is critical for the dimerization of p38α. Furthermore, p38α inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38α signaling may represent a therapeutic target for PD.

[Available on 2017-03-01]
[Indexed for MEDLINE]
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