کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6280675 1615096 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research paperOverexpression of DJ-1 protects against C2-ceramide-induced neuronal death through activation of the PI3K/AKT pathway and inhibition of autophagy
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Research paperOverexpression of DJ-1 protects against C2-ceramide-induced neuronal death through activation of the PI3K/AKT pathway and inhibition of autophagy
چکیده انگلیسی


- DJ-1 protects against C2-ceramide-induce neuronal death.
- DJ-1 prevents AKT de-phosphorylation associated to C2-ceramide exposure.
- C2-ceramide-induced autophagy is prevented by DJ-1 independently of mTOR.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. It is characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Early-onset familial forms of PD are associated with mutations in several genes, including parkin, pink1 and dj-1. DJ-1 encodes a protein whose neuroprotective function has not been completely clarified yet. We aim to understand the neuroprotective mechanisms of DJ-1, in particular, DJ-1's involvement in the regulation of the PI3K/PTEN/AKT/mTOR pathway and neuronal autophagy in a neurotoxic context induced by C2-ceramide, by using CAD cells, a murine cathecolaminergic cell line. We demonstrated that C2-ceramide induces CAD cell death associated with decreased phosphorylation of PTEN at Ser380, AKT at Ser473, and mTOR at Ser2448; and increased of autophagic flux (increased LC3-II and autophagosome formation). Additionally, we showed that overexpression of DJ-1 protects against C2-ceramide-induced neuronal death and it is not associated with change in the phosphorylation of mTOR at Ser2448. In conclusion, these data suggest that DJ-1 reinforces the PI3K/AKT survival pathway and inhibits autophagy, probably by a mechanism independent from mTOR.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 603, 31 August 2015, Pages 71-76
نویسندگان
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