Neuroprotective effect of astragalin via activating PI3K/Akt-mTOR-mediated autophagy on APP/PS1 mice

Abstract

As a small molecule flavonoid, astragalin (AST) has anti-inflammatory, anti-cancer, and anti-oxidation effects. However, the impact and molecular mechanism of AST in Alzheimer’s disease (AD) are still not clear. This study aims to investigate the neuroprotective effect and mechanism of AST on APP/PS1 mice and Aβ25-35-injured HT22 cells. In this study, we found that AST ameliorated cognitive dysfunction, reduced hippocampal neuronal damage and loss, and Aβ pathology in APP/PS1 mice. Subsequently, AST activated autophagy and up-regulated the levels of autophagic flux-related protein in APP/PS1 mice and Aβ25-35-induced injury in HT22 cells. Interestingly, AST down-regulated the phosphorylation level of PI3K/Akt-mTOR pathway-related proteins, which was reversed by autophagy inhibitors 3-Methyladenine (3-MA) or Bafilomycin A1 (Baf A1). At the same time, consistent with the impacts of Akt inhibitor MK2206 and mTOR inhibitor rapamycin, inhibited levels of autophagy in Aβ25-35-injured HT22 cells were activated by the administration of AST. Taken together, these results suggested that AST played key neuroprotective roles on AD via stimulating PI3K/Akt-mTOR pathway-mediated autophagy and autophagic flux. This study revealed a new mechanism of autophagy regulation behind the neuroprotection impact of AST for AD treatment.

Modulatory Effect of Low-Intensity Transcranial Ultrasound Stimulation on Behaviour and Neural Oscillation in Mouse Models of Alzheimer’s Disease

“…5xFAD is a new type of AD mouse model developed on the basis of APP/PS1 and has received widespread attention. In recent animal studies on AD, APP/PS1 mice was widely used as the AD model due to that they have the characteristics of AD well at the cellular and molecular levels [18][19][20]. We believe that APP/PS1 mice can meet our study.…”

“…With the accumulation of gene effects, typical features similar to AD can appear in pathology and learning cognitive abilities, effectively simulating the characteristics of AD. Many scholars have studied the treatment and pathogenesis of AD based on this model mouse, which has high application value [18][19][20]. However, it remains unclear how long-term low-intensity TUS modulates neural activity in the hippocampal brain region, which is closely related to learning and memory, of the APP/PS1 AD mouse model.…”

Autophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury

“…To elucidate the underlying mechanisms, we conducted RNA sequencing (RNA-seq) on H/R-treated PRTCs. KEGG analysis indicated that H/R activated autophagy and several well-known signaling pathways, including the hypoxia-related HIF-1 signaling, mTOR activity 24 , and PI3K/AKT 25 and MAPK 26 linked to autophagy regulation (Fig. 5a ).…”

The contribution of mitochondria-associated endoplasmic reticulum membranes (MAMs) dysfunction in Alzheimer’s disease and the potential countermeasure

“…Abnormal autophagy is involved in the development of AD ( Yuan et al, 2022 ). Activation of autophagy alleviates pathological characters and cognitive deficits in APP/PS1 mice ( Yang et al, 2023 ). The MAMs mark the starting point of autophagosome formation.…”