%0 Journal Article
%T Geniposide-mediated protection against amyloid deposition and behavioral impairment correlates with downregulation of mTOR signaling and enhanced autophagy in a mouse model of Alzheimer's disease
%A Di Zhang
%A Lin Li
%A Xiaojian Wang
%A Yueze Liu
%A Zhihua Zhang
%J Archive of "Aging (Albany NY)".
%D 2019
%R 10.18632/aging.101759
%X Geniposide, an iridoid glycoside extract from the gardenia fruit, is used in traditional Chinese medicine to alleviate symptoms of liver and inflammatory diseases. Geniposide activates GLP-1 receptors, known to modulate the activity of mechanistic target of rapamycin (mTOR), a key kinase regulating energy balance, proliferation, and survival in cells. mTOR activation inhibits autophagy, which is often disrupted in age-related diseases. Modulation of mTOR function to increase autophagy and inhibit apoptosis is involved in the protective effects of pharmacologic agents targeting diabetes and Alzheimer¡¯s disease (AD). We investigated whether such mechanism could mediate geniposide¡¯s neuroprotective effects in the APP/PS1 mouse model of AD. Eight-week treatment with geniposide improved cognitive scores in behavioral tests, reduced amyloid-¦Â 1-40 plaque deposition, and reduced soluble A¦Â1-40 and A¦Â1-42 levels in the APP/PS1 mouse brain.This also showed increased p-Akt/Akt, p-mTOR/mTOR and decreased p-4E-BP1/4E-BP1 expression, and these patterns were partially reversed by geniposide. Evidence for enhanced autophagy, denoted by increased expression of LC3-II and Beclin1, was also seen after treatment with geniposide. Our data suggests that down regulation of mTOR signaling, leading to enhanced autophagy and lysosomal clearance of A¦Â fibrils, underlies the beneficial effects of geniposide against neuropathological damage and cognitive deficits characteristic of AD
%K geniposide
%K APP/PS1 mice
%K mechanistic target of rapamycin
%K autophagy
%K Alzheimer¡¯s disease
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366989/