Mitochondriomics reveals the underlying neuroprotective mechanism of TrkB receptor agonist R13 in the 5×FAD mice.

Ting Li, Xiao Li, Xi Huang, Hao Yu, Shupeng Li, Zaijun Zhang, Yongmei Xie, Xiangrong Song, Jianjun Liu, Xifei Yang, Gongping Liu

Neuropharmacology 2022 Feb 15

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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-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. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

Ting Li, Xiao Li, Xi Huang, Hao Yu, Shupeng Li, Zaijun Zhang, Yongmei Xie, Xiangrong Song, Jianjun Liu, Xifei Yang, Gongping Liu. Mitochondriomics reveals the underlying neuroprotective mechanism of TrkB receptor agonist R13 in the 5×FAD mice. Neuropharmacology. 2022 Feb 15;204:108899