RT Journal Article
SR Electronic
T1 Mitochondriomics reveals the underlying neuoprotective mechanism of TrkB receptor agonist R13 in the 5×FAD mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.08.430227
DO 10.1101/2021.02.08.430227
A1 Xiao Li
A1 Ting Li
A1 Hao Yu
A1 Shupeng Li
A1 Zaijun Zhang
A1 Yongmei Xie
A1 Xiangrong Song
A1 Jianjun Liu
A1 Xifei Yang
A1 Gongping Liu
YR 2021
UL http://biorxiv.org/content/early/2021/02/08/2021.02.08.430227.abstract
AB 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 of mitochondriomics demonstrated that R13 promoted mitochondrial oxidative phosphorylation (OXPHOS). The functional analysis showed that R13 increased ATP levels and enhanced OXPHOS including complex I, complex II, complex III and complex IV. R13 treatment increased mitochondrial biogenesis by regulating the levels of p-AMPKα, p-CREB, PGC-1α, NRF1 and TFAM as a consequence of activation of TrkB receptor in the 5×FAD mice. Finally, R13 significantly reduced the levels of tau phosphorylation and Aβ plaque. Our data suggest that R13 may be used for treating AD via enhancing mitochondrial biogenesis and metabolism.Competing Interest StatementThe authors have declared no competing interest.