Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2024-11-13 DOI:10.1016/j.arr.2024.102578

Anna Maggiore , Valentina Latina , Maria D’Erme , Giuseppina Amadoro , Roberto Coccurello

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引用次数: 0

Abstract

Alzheimer’s Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points. Ageing, genetic and environmental risk factors, along with different clinical symptoms suggest that AD is a complex and heterogeneous disorder with multiple interconnected pathological pathways rather than a single disease entity. In the present review, we highlight and discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid and sugar signaling, and cerebrovascular damage that contribute to the onset and development of AD. We emphasize that challenging the traditional “amyloid cascade hypothesis” may improve our understanding of this age-related complex syndrome and help fight the progressive cognitive decline in AD.

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阿尔茨海默病中与淀粉样β和 Tau 蛋白失衡有关的非经典途径：叙述性综述。

阿尔茨海默病（AD）是老年人中最常见的痴呆症。由于全球老龄化人口不断增加，这种疾病给医疗保健系统、社会和经济造成了沉重负担。淀粉样 beta（Aβ）斑块和 tau 蛋白神经纤维缠结是这种破坏性神经退行性疾病的两大特征，目前旨在减少这两种疾病的药物或生物活性化合物的试验在神经病理学结果方面没有取得显著效果，也没有达到预期的临床终点。年龄增长、遗传和环境风险因素以及不同的临床症状表明，AD 是一种复杂的异质性疾病，具有多种相互关联的病理途径，而非单一的疾病实体。在本综述中，我们重点讨论了导致 AD 发病和发展的各种非典型的、不依赖于 Aβ 的机制，如神经胶质增生、不健康的饮食摄入、脂质和糖类信号转导以及脑血管损伤。我们强调，挑战传统的 "淀粉样蛋白级联假说 "可能会提高我们对这一与年龄相关的复杂综合征的认识，并有助于对抗注意力缺失症的渐进性认知衰退。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.