The neuroprotective effects of alpha-lipoic acid on an experimental model of Alzheimer's disease in PC12 cells
Autor: | Fangyan Hu, Shuxia Xing, Ding‐Xin Long, Xinrong Pei, Xianglu Huang, Feiya Luo, Xiao‐Ling Li |
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Rok vydání: | 2021 |
Předmět: |
Amyloid beta
010501 environmental sciences Pharmacology Toxicology 01 natural sciences Neuroprotection PC12 Cells Pathogenesis 03 medical and health sciences Alzheimer Disease medicine Animals 030304 developmental biology 0105 earth and related environmental sciences chemistry.chemical_classification 0303 health sciences Reactive oxygen species Amyloid beta-Peptides biology Thioctic Acid Neurotoxicity Wnt signaling pathway medicine.disease Rats Disease Models Animal Neuroprotective Agents chemistry Apoptosis biology.protein Alzheimer's disease |
Zdroj: | Journal of applied toxicology : JATREFERENCES. 42(2) |
ISSN: | 1099-1263 |
Popis: | With the growth of the aging population, the prevalence of Alzheimer's disease (AD) has increased and influenced the work and daily life of AD patients, imposing a heavy burden on society and the patients' families. AD is a progressive disease with a long duration, and the pathogenesis is very complicated. Here, we found that alpha-lipoic acid (LA), an endogenous, naturally synthesized compound, could attenuate amyloid beta fragment (Aβ25-35 )-induced PC12 cell toxicity. Aβ25-35 treatment largely decreased the viability of PC12 cells, increased reactive oxygen species (ROS) levels, and increased the percentage of apoptotic cells, which were accompanied by changes in the expression of the apoptosis-related genes. Further, the Wnt pathway was inactivated, and the expression of Wnt pathway-related proteins such as Frizzled2, GSK3β, and phosphorylated GSK3β were dysregulated after Aβ25-35 treatment. LA efficiently attenuated Aβ25-35 -induced PC12 cell apoptosis and downregulated the phosphorylation-mediated degradation of β-catenin as well as GSK3β. Our results demonstrate that LA rescues Aβ25-35 -induced neurocytotoxicity through the Wnt-β-catenin pathway. |
Databáze: | OpenAIRE |
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