Publication: Huperzine A Regulates the Physiological Homeostasis of Amyloid Precursor Protein Proteolysis and Tau Protein Conformation—A Computational and Experimental Investigation
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Issued Date
2024-07-01
Resource Type
eISSN
20797737
Scopus ID
2-s2.0-85199640415
Journal Title
Biology
Volume
13
Issue
7
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biology Vol.13 No.7 (2024)
Suggested Citation
Wongjaikam S., Nopparat C., Boontem P., Panmanee J., Thasana N., Shukla M., Govitrapong P. Huperzine A Regulates the Physiological Homeostasis of Amyloid Precursor Protein Proteolysis and Tau Protein Conformation—A Computational and Experimental Investigation. Biology Vol.13 No.7 (2024). doi:10.3390/biology13070518 Retrieved from: https://hdl.handle.net/20.500.14740/20656
Corresponding Author(s)
Other Contributor(s)
Abstract
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.