Journal
NEUROPHARMACOLOGY
Volume 204, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2021.108899
Keywords
Proteomics; OXPHOS; Mitochondrial biogenesis; TrkB
Categories
Funding
- Natural Science Foundation of China [81673134, 81870846]
- Ministry of Science and Technology of China [2016YFC13058001]
- Guangdong Provincial Key ST Program [2018B030336001]
- Sanming Project of Medicine in Shenzhen [SZSM201611090]
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The study showed that R13 has significant effects on mitochondrial protein expression profile, promoting oxidative phosphorylation, increasing ATP levels and mitochondrial biogenesis, while reducing tau phosphorylation and plaque levels.
Decreased energy metabolism and mitochondrial biogenesis defects are implicated in the pathogenesis of Alzheimer's disease (AD). In present study, mitochondriomics analysis revealed significant effects of R13, a prodrug of 7,8-dihydroxyflavone, on mitochondrial protein expression profile, including the proteins related to the biological processes: fatty acid beta-oxidation, fatty acid metabolic process, mitochondrial electron transport, and mitochondrial respiratory chain. Cluster analysis demonstrated that R13 promoted mitochondrial oxidative phosphorylation (OXPHOS). The functional analysis showed that R13 increased ATP levels and enhanced OXPHOS including complex I, II, III and IV. R13 treatment increased mitochondrial biogenesis by regulating the levels of p-AMPK alpha, p-CREB, PGC-1 alpha, NRF1 and TFAM as a consequence of activation of TrkB receptor in the 5 x FAD mice. Finally, R13 significantly reduced the levels of tau phosphorylation and All plaque. Our data suggest that R13 may be used for treating AD via enhancing mitochondrial biogenesis and metabolism.
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