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阿尔茨海默病:探索病理生理假说及机器学习在药物发现中的作用

Alzheimer's Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery.

作者信息

Dominguez-Gortaire Jose, Ruiz Alejandra, Porto-Pazos Ana Belen, Rodriguez-Yanez Santiago, Cedron Francisco

机构信息

Department of Computer Science and Information Technologies, Faculty of Computer Science, Universidade da Coruña, 15071 A Coruña, Spain.

Faculty of Biological Sciences, Universidad Central del Ecuador, Quito 170136, Ecuador.

出版信息

Int J Mol Sci. 2025 Jan 24;26(3):1004. doi: 10.3390/ijms26031004.

Abstract

Alzheimer's disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from the traditionally dominant amyloid hypothesis toward a multifactorial understanding of the disease. Emerging evidence suggests that while amyloid-beta (β) accumulation is central to AD, it may not be the primary driver but rather part of a broader pathogenic process. Novel hypotheses have been proposed, including the role of tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, the gut-brain axis and epigenetic modifications have gained attention as potential contributors to AD progression. The limitations of existing therapies underscore the need for innovative strategies. This study explores the integration of machine learning (ML) in drug discovery to accelerate the identification of novel targets and drug candidates. ML offers the ability to navigate AD's complexity, enabling rapid analysis of extensive datasets and optimizing clinical trial design. The synergy between these themes presents a promising future for more effective AD treatments.

摘要

阿尔茨海默病(AD)是一种主要的神经退行性痴呆,其复杂的病理生理学对当前的治疗方法构成挑战。最近的进展已将焦点从传统上占主导地位的淀粉样蛋白假说转向对该疾病的多因素理解。新出现的证据表明,虽然β-淀粉样蛋白(Aβ)积累是AD的核心,但它可能不是主要驱动因素,而是更广泛致病过程的一部分。已经提出了新的假说,包括tau蛋白异常、线粒体功能障碍和慢性神经炎症的作用。此外,肠-脑轴和表观遗传修饰作为AD进展的潜在促成因素也受到了关注。现有疗法的局限性凸显了创新策略的必要性。本研究探讨了机器学习(ML)在药物发现中的整合,以加速新型靶点和候选药物的识别。ML能够应对AD的复杂性,实现对大量数据集的快速分析并优化临床试验设计。这些主题之间的协同作用为更有效的AD治疗展现了充满希望的未来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9feb/11816687/5b3055618b46/ijms-26-01004-g001.jpg

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