β‑asarone modulates Beclin‑1, LC3 and p62 expression to attenuate Aβ40 and Aβ42 levels in APP/PS1 transgenic mice with Alzheimer's disease

Abstract

alzheimer's disease (ad) is a common neurodegenerative disease in the elderly population. autophagy is a well-known regulator of neurodegenerative diseases and β-asarone has been discovered to have certain neuropharmacological effects. Thus, the present study aimed to analyze the potential effects of β-asarone in ad and its possible mechanism of action in relation to autophagy. The present study investigated the effects of β-asarone on the number of senile plaques and amyloid β(aβ) 40 , aβ 42 , amyloid precursor protein (aPP) and Beclin-1 mrna levels in the hippocampus of aPP/presenilin-1 (PS1) transgenic mice. The possible mechanism of β-asarone on autophagy-related proteins, including Beclin-1, light chain (lc)3a, lc3B and p62 levels, and the number of autophagosomes was also investigated. Mice were divided into a normal control group, a model group, a β-asarone-treated group, a 3-Ma-treated group and a rapamycin-treated group. Treatments were continuously administered to all mice for 30 days by intragastric administration. The mice, including those in the normal and model control groups, were given equal volumes of saline. it was demonstrated that β-asarone treatment reduced the number of senile plaques and autophagosomes, and decreased aβ 40 , aβ 42 , aPP and Beclin-1 expression in the hippocampus of model mice compared with untreated model mice. β-asarone also inhibited lc3a/B expression levels, but increased p62 expression. it was deduced that the neuroprotective effects of β-asarone in aPP/PS1 transgenic mice resulted from its inhibition of autophagy. in conclusion, the data suggested that β-asarone should be explored further as a potential therapeutic agent in ad.

β-Asarone Attenuates Aβ-Induced Neuronal Damage in PC12 Cells Overexpressing APPswe by Restoring Autophagic Flux

“…The decrease in Beclin-1 may be due to the elimination of Aβ 1-42 from cells due to β-asarone. When the cause of stress state was relieved, the expression of Beclin-1 tended to return to normal level ( Deng et al, 2020 ). The decreased levels of p62 and LC3-Ⅱ suggest that the number of autophagosomes decreased, indicating that β-asarone promoted the clearance of Aβ 1-42 by promoting autophagosome-lysosome fusion or autolysosomal degradation ( Barbero-Camps et al, 2018 ).…”

p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

“…Restoration of Aβ-induced mitochondrial dysfunction and impaired mitophagy was obtained by overexpressing parkin [ 107 ], an ubiquitin ligase that will be described in the next subsection. Moreover, in this connection, autophagy inhibition has been proposed as a tool to attenuate Aβ toxicity and neurodegeneration in Alzheimer transgenic mice models [ 108 ].…”

Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders

“…A very recent study found that α-asarone potentially targets the Aβ and tau pathology pathways by inhibiting Aβ 42 aggregation, in addition to inhibiting tau phosphorylation, resulting in improved spatial learning memory in APP/presenilin-1 (PS1) transgenic mice [ 28 ] ( Figure 3 ). Another study demonstrated that treatment with β-asarone reduced the number of senile plaques and decreased Aβ 40 , Aβ 42 , and APP expression levels in the hippocampus of APP/PS1 transgenic mice [ 85 ]. Moreover, β-asarone displayed a significant therapeutic effect against toxic protein deposition and increased the expression of the presynaptic protein synapsin 1 (SYN1), which should remove toxic superoxide anion radicals produced in cells [ 114 ].…”