Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The aggregation of Aβ peptides, Aβ1-42 in particular, is thought to be a fundamental pathogenic mechanism leading to the neuronal damage in AD. Recently, monosialoganglioside GM1 is reported to possess pivotal neuroprotection in neurodegenerative diseases. Previous studies have focused on the conformational dynamics and the biochemical interaction of the amyloid-peptide with the GM1 ganglioside, as well as the protective effect of GM1 on cognition. However, the phenomenon of autophagy with regard to neuronal dysfunction in AD is less investigated. In the present study, GM1 treatment were investigated in an AD mouse model and cultured PC12 dells to examine cognition-protective and neuroprotective effects of GM1. Furthermore, GM1 was found to induce autophagy via testing light chain 3 (LC3), Beclin1, neighbor of BRCA1 gene 1 protein and p62 (a substrate of LC3). Chloroquine, an inhibitor of lysosomal, was used to exclude the interference of lysosome, which could fuse with autophagosome and then clear it. In the presence of the inhibitor of autophagy (3-methyladenine; 3-MA), the protective effect of GM1 on PC12 cells in Aβ (1-42) induced toxic conditions was diminished. Interestingly, the expression of histone deacetylase 1 was increased in PC12 cells when treated with GM1, indicating that autophagy might be activated by GM1 through a pathway integrates protein acetylation. This study provides a novel insight into the protective role of GM1 against Aβ (1-42)-induced neurotoxicity via enhancing autophagy.
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Acknowledgements
This work was supported by Guangdong Provincial Major Science and Technology for Special Program of China (No. 2012A080202017), the Characteristic key Discipline Construction Fund of Chinese Internal Medicine of Guangzhou University of Chinese Medicine and South China Chinese Medicine Collaborative Innovation Center (No. A1-AFD01514A05), the Doctoral Fund of Education Ministry of China (No. 20134425110003).
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Ruwei Dai and Shijie Zhang have contributed equally to this work.
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Dai, R., Zhang, S., Duan, W. et al. Enhanced Autophagy Contributes to Protective Effects of GM1 Ganglioside Against Aβ1-42-Induced Neurotoxicity and Cognitive Deficits. Neurochem Res 42, 2417–2426 (2017). https://doi.org/10.1007/s11064-017-2266-0
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DOI: https://doi.org/10.1007/s11064-017-2266-0