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P2‐176: IDENTIFICATION OF AN EXPERIMENTAL DRUG THAT ENHANCES BRAIN SIRTUIN 1 LEVELS AND IMPROVES COGNITION AS A POTENTIAL NEW THERAPEUTIC FOR AD
Author(s) -
Campagna Jesus J.,
Spilman Patricia,
Elias Chris Jean,
Zhu Chunni,
Bilousova Tina,
Jun Michael,
Bai Dongsheng,
Pham Johnny,
Kim Young Sug,
Bredesen Dale E.,
Jung Michael,
John Varghese
Publication year - 2019
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.2019.06.2583
Subject(s) - sirt2 , sirtuin , pharmacology , vesicular acetylcholine transporter , sirtuin 1 , genetically modified mouse , transgene , in vivo , in vitro , drug , chemistry , medicine , biology , biochemistry , acetylcholine , downregulation and upregulation , gene , microbiology and biotechnology , acetylation , choline acetyltransferase
oscillation, here we studied the mechanism underlying the potential effect of miR-219 shortage in circadian alterations and neurodegeneration. Methods: Here we performed locomotion and sleep analysis in L/D and D/D conditions in miR-219 mutant flies. We studied mRNA oscillatory expression of tau, GSK3beta, and core clock genes.We further analyzed protein synthesis and its circadian turnover. Results: We observed circadian rhythm alterations in miR-219 mutants that were age-dependent and that appeared enhanced in older flies. These alterations correlate with aberrant clock protein turnover in PDF-neurons. Notably, miR-219 knockout flies also showed age-related alterations in sleep. Conclusions: Our data reveal a novel role of miR-219 in driving circadian/ sleep alterations and neurodegeneration. Altogether, these studies are starting to unravel mechanistic roles for microRNAs in neuronal physiology and pathology.