Genipin Attenuates Tau Phosphorylation and Aβ Levels in Cellular Models of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a devastating brain disorder characterized by neurofibrillary tangles and amyloid plaques. Inhibiting Tau protein and amyloid-beta (Aβ) production or removing these molecules is considered potential therapeutic strategies for AD. Genipin is an aglycone and is isolated from the extract of Gardenia jasminoides Ellis fruit. In this study, the effect and molecular mechanisms of genipin on the inhibition of Tau aggregation and Aβ generation were investigated. The results showed that genipin bound to Tau and protected against heparin-induced Tau fibril formation. Moreover, genipin suppressed Tau phosphorylation probably by downregulating the expression of CDK5 and GSK-3β, and activated mTOR-dependent autophagy via the SIRT1/LKB1/AMPK signaling pathway in Tau-overexpressing cells. In addition, genipin decreased Aβ production by inhibiting BACE1 expression through the PERK/eIF2α signaling pathway in N2a/SweAPP cells. These data indicated that genipin could effectively lead to a significant reduction of phosphorylated Tau level and Aβ generation in vitro, suggesting that genipin might be developed into an effective therapeutic complement or a potential nutraceutical for preventing AD.

• Authors: Meiting Li, Nan Cai, Liang Gu, Lijun Yao, Decheng Bi, Weishan Fang, Zhijian Lin, Yan Wu, Hong Xu, Hui Li, Zhangli Hu, Xu Xu
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 58 Issue 8 Pg. 4134-4144 (Aug 2021) ISSN: 1559-1182 [Electronic] United States
• PMID: 33948899 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Amyloid beta-Peptides
• Iridoids
• MAPT protein, human
• tau Proteins
• genipin

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism)
• Animals
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• HEK293 Cells
• Humans
• Iridoids (pharmacology)
• Mice
• Mice, Transgenic
• Phosphorylation (drug effects, physiology)
• Protein Structure, Tertiary
• tau Proteins (antagonists & inhibitors, metabolism)