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P2‐010: DEHYDROEPIANDROSTERONE MODULATES MEMBRANE FUNCTIONS, ANTIOXIDANT ENZYMES, AND BEHAVIORAL CHANGES IN BRAIN OF AGING FEMALE RATS
Author(s) -
Kumar Pardeep,
Kale R.K.,
Baquer Najma
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.683
Subject(s) - dehydroepiandrosterone , medicine , endocrinology , acetylcholinesterase , lipid peroxidation , antioxidant , aging brain , superoxide dismutase , chemistry , hormone , biology , oxidative stress , biochemistry , enzyme , androgen , disease
find an interesting feed-forward regulatory mechanism between FoxO1, a direct target of Akt and TRB3 in Ab-treated cells. These two proteins control the expression of one another as observed by immunocytochemical staining and western blot analysis. We further confirm the physical binding between FoxO1 and TRB3 promoter by chromatin immunoprecipitation. We also observed decreased expression of FoxO1 regulated, apoptotic gene, Bim upon TRB3 downregulation. Furthermore, we find that TRB3 regulates autophagy in neurons induced by (Ab)1-42. Downregulating TRB3 leads to suppression of autophagy as observed by decreased LC3 staining. It also leads to increased phosphorylation of mTOR which in turn inhibits autophagy. We deduce that TRB3may be regulating autophagy in neurons via the Akt/mTOR pathway. Furthermore silencing of TRB3 gene by shRNA provides significant protection to primary cortical neurons against Ab insult.Conclusions: Thus this study indicates that TRB3may be a potential target for therapeutic intervention in AD.