| First Author | Wu R | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 3 | Pages | 542-52 |
| PubMed ID | 26517532 | Mgi Jnum | J:258918 |
| Mgi Id | MGI:6140891 | Doi | 10.1038/cdd.2015.135 |
| Citation | Wu R, et al. (2016) c-Abl-p38alpha signaling plays an important role in MPTP-induced neuronal death. Cell Death Differ 23(3):542-52 |
| abstractText | 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 p38alpha as a major substrate of c-Abl both in vitro and in vivo and c-Abl-mediated phosphorylation is critical for the dimerization of p38alpha. Furthermore, p38alpha inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38alpha signaling may represent a therapeutic target for PD. |
