Repurposing dapagliflozin for Alzheimer's disease: a mechanistic exploration

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2024-12-18 DOI:10.1186/s43094-024-00751-w

Marwa M. Saeed

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引用次数: 0

Abstract

Background

Several researches describe Alzheimer’s disease (AD) as Type-III diabetes mellitus due to shared pathophysiological mechanisms between AD and DM and the fact that one disease can increase the incidence of the other. Therefore, keeping glucose level under control protects the brain from its harmful effects and delays the incidence of AD in susceptible individuals by using anti-diabetic agents. Several anti-diabetic classes were explored for their protective effect against AD, among them that attracted more attention was sodium–glucose cotransporter inhibitor dapagliflozin (DAPA).

Main body of the abstract

This review aims at illustrating various protective mechanisms that DAPA proved to exert on cognition and memory. DAPA showed promising results by its influence on behavioral parameters highlighted enhancement of both spatial and non-spatial learning and memory, in addition to ameliorating associated anxiety by its effect on various neurotransmitters. DAPA succeeded in promoting neurogenesis, synaptic plasticity, and synaptic density, and managed to demonstrate anti-inflammatory, antioxidant, and antiapoptotic properties. Moreover, DAPA enhanced the activity of mitochondria and promoted autophagy, in addition to its impact on the PI3K/AKT/mTOR and Wnt/β-catenin signaling pathways.

Short conclusion

DAPA showed promising results in different AD models to enhance memory and improve cognitive deficits.

Graphical abstract

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重新利用达格列净治疗阿尔茨海默病：机制探索

一些研究将阿尔茨海默病（AD）描述为iii型糖尿病，因为AD和DM之间有共同的病理生理机制，而且一种疾病可以增加另一种疾病的发病率。因此，控制血糖水平可以保护大脑免受其有害影响，并通过使用抗糖尿病药物延缓易感个体AD的发生。研究了几种抗糖尿病药物对AD的保护作用，其中最受关注的是钠-葡萄糖共转运蛋白抑制剂dapagliflozin （DAPA）。本文旨在阐述DAPA对认知和记忆的各种保护机制。DAPA通过其对行为参数的影响显示出令人鼓舞的结果，其中包括空间和非空间学习和记忆的增强，以及通过其对各种神经递质的作用改善相关焦虑。DAPA成功地促进了神经发生、突触可塑性和突触密度，并成功地证明了抗炎、抗氧化和抗凋亡的特性。此外，DAPA除了影响PI3K/AKT/mTOR和Wnt/β-catenin信号通路外，还能增强线粒体活性，促进自噬。结论dapa在不同AD模型中具有增强记忆和改善认知缺陷的良好效果。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

0.00%

发文量

审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.