Mitochondriomics reveals the underlying neuroprotective mechanism of TrkB receptor agonist R13 in the 5xFAD mice

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.

Automated summary

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.