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[P2–130]: AR‐A014418, A GSK‐3β INHIBITOR, ATTENUATES ALZHEIMER'S‐ LIKE PATHOLOGY IN HIGH FAT DIET‐INDUCED COGNITIVE DEFICIT IN MICE
Author(s) -
Sharma Sorabh,
Taliyan Rajeev
Publication year - 2017
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.2017.06.780
Subject(s) - endocrinology , medicine , gsk 3 , morris water navigation task , insulin resistance , glycogen synthase , tau protein , hyperphosphorylation , hippocampal formation , cognitive decline , glial fibrillary acidic protein , hippocampus , chemistry , alzheimer's disease , insulin , kinase , dementia , disease , biochemistry , immunohistochemistry
the underlying mechanisms involved. Results:Our ChIP analysis and luciferase reporter assays show that palmitate-induced SREBP1 activation directly regulates BACE1 expression at the transcriptional level. Knocking-down or ectopic expression of the dominant negative SREBP1 mutant significantly mitigated the palmitate-induced BACE1 expression and subsequent Ab genesis. Conclusions: Our study elucidates a novel signaling pathway and SREBP1 as a unique downstream effector of palmitate-induced up-regulation in BACE1 expression and subsequent Ab genesis.