| Autor: |
Wongjaikam, Suwakon, Nopparat, Chutikorn, Boontem, Parichart, Panmanee, Jiraporn, Thasana, Nopporn, Shukla, Mayuri, Govitrapong, Piyarat |
| Předmět: |
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| Zdroj: |
Biology (2079-7737); Jul2024, Vol. 13 Issue 7, p518, 16p |
| Abstrakt: |
Simple Summary: Alzheimer's disease is a chronic neurodegenerative disorder that causes brain shrinkage and cellular death. The pathological changes like formation of amyloid plaques and aggregation of hyperphosphorylated tau in the brain begin years before the clinical symptoms appear. Moreover, there has been a drastic increment in the number of people affected by this disease. Unfortunately, there is no cure for Alzheimer's. In this scenario, natural compounds with potent neuroprotective properties and minimal side effects hold promise. Therefore, the present study investigated the effects of Huperzine A (an alkaloid isolated from the moss Huperzia serrata) on the amyloid processing and tau conformations under physiological conditions with an aim of developing a preventive rather than curative approach. The outcome of this study shows that Huperzine A can significantly modulate the amyloid-β and tau processing, suggesting that it could protect the nerve cells, slow cognitive decline, and improve memory. We further suggest that advancement of Huperzine A as a general therapeutic agent might alleviate the socio-economic burden related to the progressive debilitating nature of this disease. The beneficial actions of the natural compound Huperzine A (Hup A) against age-associated learning and memory deficits promote this compound as a nootropic agent. Alzheimer's disease (AD) pathophysiology is characterized by the accumulation of amyloid beta (Aβ). Toxic Aβ oligomers account for the cognitive dysfunctions much before the pathological lesions are manifested in the brain. In the present study, we investigated the effects of Hup A on amyloid precursor protein (APP) proteolysis in SH-SY5Y neuroblastoma cells. Hup A downregulated the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) levels but augmented the levels of A disintegrin and metalloproteinase 10 (ADAM10) with significant decrement in the Aβ levels. We herein report for the first time an in silico molecular docking analysis that revealed that Hup A binds to the functionally active site of BACE1. We further analyzed the effect of Hup A on glycogen synthase kinase-3 β (GSK3β) and phosphorylation status of tau. In this scenario, based on the current observations, we propose that Hup A is a potent regulator of APP processing and capable of modulating tau homeostasis under physiological conditions holding immense potential in preventing and treating AD like disorders. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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