Abstract

Alzheimer's disease (AD) is one of the most common types of dementia that causes memory, thinking, and behavior problems. The most important feature of AD is the gradual irreversible loss of cognitive ability through the formation of amyloid β (Aβ) plaques and neurofibrillary tangles composed of tau protein. The metabolism of Aβ and tau proteins is closely related to and is affected by autophagy. Current research speculates that autophagy dysfunction leads to an increase in harmful proteins in AD. β-Asarone is the main constituent of Acorus tatarinowii Schott and has important effects on the central nervous system. In this paper, we primarily explored the effects of β-asarone on the clearance of noxious proteins and the associated potential mechanisms via autophagy in a PC12 cell AD model. A CCK-8 assay and LDH experiments were used to assess cell viability/toxicity, and SPiDER-βGal was used to detect cellular senescence. The important proteins associated with the pathogenesis of AD including APP, PS1, Aβ, BACE1, and SYN1 were analyzed by immunofluorescence (IF) and Western blot analysis. Antimycin A (A3) and cyclosporine A (CSA) were selected as the activators and inhibitors of autophagy, respectively. LC3, BECN, P62, PINK1, and Parkin protein expression were also examined by IF and Western blot analysis. The data showed that β-asarone administration significantly dose-dependently increased cell proliferation and decreased cytotoxicity; moreover, β-asarone inhibited SA-βGal and improved cell senescence. The results further showed that, compared to the model, APP, PS1, Aβ, BACE1, and p62 were reduced, while SYN1, BECN1, and LC3 were increased after treatment with β-asarone. The results of Canonical Correlation Analysis (CCA) showed a highly significant relationship between the pathological factors of AD and the protein expression of autophagy. In conclusion, our study demonstrated that β-asarone can inhibit Aβ, and this effect may occur by promoting autophagy in a cell model of AD.

Highlights

  • Alzheimer's disease (AD) is the most frequent cause of dementia, and this disease is gradually escalating into a global epidemic among older adults

  • We propose that b-asarone could protect a PC12 cell model against Ab1-42 damage, and this process should occur by promoting autophagy

  • To establish the AD cell model, we cultured PC12 cells in vitro, and Ab1-42 was added into the medium in different concentrations and time points

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Summary

Introduction

Alzheimer's disease (AD) is the most frequent cause of dementia, and this disease is gradually escalating into a global epidemic among older adults. The major neuropathological features of AD are widely described: amyloid b (Ab) plaques and neurofibrillary tangles, but no treatment has changed its progression (LoeraValencia et al, 2019; Reddy et al, 2019). Apart from these clear pathological lesions, the brain's immune response undergoes dramatic changes, including dramatic changes in microglia and astrocyte phenotypes (Henstridge et al, 2019). Research on the pathogenesis of AD continues to be controversial, the Ab peptide is considered to be a central player (Vassa, 2004). Donepezil (Aricept) is a centrally acting reversible acetyl cholinesterase (AChE) inhibitor which could increase the content of ACh and improving the cognitive function of patients with AD (Reardon, 2018)

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