Insights Into the Therapeutic Potential of SIRT1-modifying Compounds for Alzheimer’s Disease: A Focus on Molecular Mechanisms

IF 2.7 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2025-02-25 DOI:10.1007/s12031-025-02324-9

Dhyauldeen Aftan AlHayani, Aziz Kubaev, Subasini Uthirapathy, Viralkumar Mandaliya, Suhas Ballal, Rishiv Kalia, Renu Arya, Baneen C. Gabble, Mohammed Qasim Alasheqi, Abed J. Kadhim

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting patients’ quality of life. Recent studies have highlighted the roles of sirtuin 1 (SIRT1), a NAD + -dependent deacetylase, in regulating various biological pathways associated with AD pathology, including amyloid-beta metabolism, tau hyperphosphorylation, and neuroinflammation. This review focuses on the therapeutic potential of synthetic and natural compounds that modulate SIRT1 levels, emphasizing their molecular mechanisms of action. We explore a range of SIRT1-modifying agents, including polyphenols such as resveratrol, as well as synthetic analogs and novel pharmaceuticals that aim to enhance SIRT1 activity. Additionally, we discuss emerging innovative therapies, including pharmacological agents that improve SIRT1 signaling through mechanisms like photobiomodulation and nutritional interventions. These compounds not only target SIRT1 but also integrate into broader metabolic and neuroprotective pathways, presenting a promising approach to ameliorating AD symptoms. By elucidating the intricate interactions between SIRT1-modifying compounds and their effects on AD pathology, this review aims to advance the understanding of potential therapeutic strategies that could delay or prevent the progression of AD.

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sirt1修饰化合物治疗阿尔茨海默病的潜力：关注分子机制

阿尔茨海默病（AD）是一种进行性神经退行性疾病，以认知能力下降和记忆丧失为特征，严重影响患者的生活质量。最近的研究强调了SIRT1 （SIRT1）的作用，SIRT1是一种NAD +依赖的去乙酰化酶，在调节与AD病理相关的各种生物途径中，包括淀粉样蛋白代谢、tau过度磷酸化和神经炎症。本文综述了调节SIRT1水平的合成和天然化合物的治疗潜力，并强调了它们的分子作用机制。我们探索了一系列SIRT1修饰剂，包括多酚类物质如白藜芦醇，以及旨在增强SIRT1活性的合成类似物和新型药物。此外，我们还讨论了新兴的创新疗法，包括通过光生物调节和营养干预等机制改善SIRT1信号的药物。这些化合物不仅靶向SIRT1，还整合到更广泛的代谢和神经保护途径中，为改善AD症状提供了一种有希望的方法。通过阐明sirt1修饰化合物之间复杂的相互作用及其对AD病理的影响，本综述旨在促进对可能延缓或预防AD进展的潜在治疗策略的理解。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.