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针对tau蛋白过度磷酸化诱导的聚集体的天然产物:阿尔茨海默病的潜在疗法。

Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.

作者信息

Basurto-Islas Gustavo, Diaz Maximiliano Caye, Ocampo Lizeth M Zavala, Martínez-Herrera Melchor, López-Camacho Perla Y

机构信息

División de Ciencias e Ingenierías, Universidad de Guanajuato, León, Guanajuato, Mexico.

Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana Cuajimalpa, Ciudad de México, Mexico.

出版信息

Arch Pharm (Weinheim). 2025 Jan;358(1):e2400721. doi: 10.1002/ardp.202400721.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairments and is considered the most prevalent form of dementia. Among the contributing factors to AD lies the hyperphosphorylation of the microtubule-associated protein tau. Phosphorylated tau reduces its affinity for microtubules and triggers other posttranslational modifications that result in its aggregation and assembly into filaments. These structures progressively accumulate within neurons leading to neurodegeneration. While current AD medications often involve undesirable side effects, the exploration of natural products as a potential therapeutic alternative has gained considerable attention. Numerous compounds have shown potential capacity for reducing tau pathology through different mechanisms, such as inhibiting kinases to reduce tau hyperphosphorylation, enhancing phosphatase activity, and blocking fibril formation. Since tau hyperphosphorylation-induced aggregation is pivotal in AD onset, this review aims to elucidate the potential of natural products in modulating this crucial molecular mechanism.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征为认知能力下降和记忆障碍,被认为是最常见的痴呆形式。在导致AD的因素中,微管相关蛋白tau的过度磷酸化是其中之一。磷酸化的tau降低了其与微管的亲和力,并引发其他翻译后修饰,导致其聚集并组装成细丝。这些结构在神经元内逐渐积累,导致神经退行性变。虽然目前的AD药物往往存在不良副作用,但将天然产物作为一种潜在的治疗选择进行探索已受到相当大的关注。许多化合物已显示出通过不同机制降低tau病理学的潜在能力,例如抑制激酶以减少tau过度磷酸化、增强磷酸酶活性以及阻止原纤维形成。由于tau过度磷酸化诱导的聚集在AD发病中起关键作用,本综述旨在阐明天然产物在调节这一关键分子机制方面的潜力。

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