Aniketh Naidu, Bret Silverglate, Mary Silverglate, George T Grossberg
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引用次数: 0
Abstract
Introduction: BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) inhibitors have shown promise in treating Alzheimer's disease (AD) by reducing amyloid-beta (Aβ) production. However, clinical trials of inhibitors such as atabecestat, verubecestat, and lanabecestat have faced challenges, including limited efficacy and significant adverse effects.
Areas covered: This narrative review discusses randomized-controlled trials of BACE1 inhibitors. Literature searches were conducted using PubMed and Web of Science for studies from 2010 to 2024. Association with BACE1's widespread expression beyond the brain shows adverse effects such as anxiety, depressive symptoms, and hepatotoxicity.
Expert opinion: The trial results underscore the need for CNS-specific BACE1 inhibitors to reduce adverse effects. Future research should focus on optimizing drug design and identifying additional therapeutic avenues, such as prostate cancer and insulin resistance.
BACE1 （β位点淀粉样蛋白前体蛋白切割酶1）抑制剂通过减少β淀粉样蛋白（Aβ）的产生，显示出治疗阿尔茨海默病（AD）的希望。然而，阿他贝司他、verubecestat和lanabecestat等抑制剂的临床试验面临着挑战，包括有限的疗效和显著的不良反应。涵盖领域：这篇叙述性综述讨论了BACE1抑制剂的随机对照试验。使用PubMed和Web of Science对2010年至2024年的研究进行文献检索。与BACE1在大脑之外广泛表达的关联显示出诸如焦虑、抑郁症状和肝毒性等不良反应。专家意见：试验结果强调需要cns特异性BACE1抑制剂来减少不良反应。未来的研究应集中在优化药物设计和确定额外的治疗途径，如前列腺癌和胰岛素抵抗。
期刊介绍：
Expert Opinion on Drug Safety ranks #62 of 216 in the Pharmacology & Pharmacy category in the 2008 ISI Journal Citation Reports.
Expert Opinion on Drug Safety (ISSN 1474-0338 [print], 1744-764X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of drug safety and original papers on the clinical implications of drug treatment safety issues, providing expert opinion on the scope for future development.
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