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达格列净在阿尔茨海默病中的作用和机制:综述。

The role and mechanism of dapagliflozin in Alzheimer disease: A review.

机构信息

Department of Geriatrics, Hunan Provincial People's Hospital Hunan Normal University First Affiliated Hospital, Changsha, China.

出版信息

Medicine (Baltimore). 2024 Sep 27;103(39):e39687. doi: 10.1097/MD.0000000000039687.

Abstract

Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.

摘要

阿尔茨海默病(AD)是主要的痴呆类型,其主要特征是多个领域的认知功能障碍。由于潜在风险、适用性有限、成本高、副作用大以及患者顺应性差,目前用于 AD 的药物并未达到预期的临床疗效。然而,最近的研究结果带来了新的希望,表明钠-葡萄糖共转运蛋白 2 抑制剂(SGLT-2i)可能具有神经保护特性,为 AD 的治疗开辟了新的途径。本综述深入探讨了 SGLT-2i 在 AD 中的多种作用机制,包括抗氧化应激、抗神经炎症、自噬上调、抗细胞凋亡、乙酰胆碱酯酶抑制剂活性以及保护内皮细胞免受动脉粥样硬化和血脑屏障损伤等。此外,还概述了该药物在临床研究方面的最新进展。这些发现表明,鉴于 SGLT-2i 具有多种功能作用,它有望成为治疗 AD 的关键候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3db6/11441869/e5ecc04d1766/medi-103-e39687-g001.jpg

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