The duality of amyloid-β: its role in normal and Alzheimer's disease states.

IF 3.3 3区 医学 Q2 NEUROSCIENCES
Ali Azargoonjahromi
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引用次数: 0

Abstract

Alzheimer's disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of the brain. A key characteristic of AD is the accumulation of amyloid-beta (Aβ) plaques, which play pivotal roles in disease progression. These plaques initiate a cascade of events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial dysfunction, and disrupted calcium homeostasis. Aβ accumulation is also closely associated with other hallmark features of AD, underscoring its significance. Aβ is generated through cleavage of the amyloid precursor protein (APP) and plays a dual role depending on its processing pathway. The non-amyloidogenic pathway reduces Aβ production and has neuroprotective and anti-inflammatory effects, whereas the amyloidogenic pathway leads to the production of Aβ peptides, including Aβ40 and Aβ42, which contribute to neurodegeneration and toxic effects in AD. Understanding the multifaceted role of Aβ, particularly in AD, is crucial for developing effective therapeutic strategies that target Aβ metabolism, aggregation, and clearance with the aim of mitigating the detrimental consequences of the disease. This review aims to explore the mechanisms and functions of Aβ under normal and abnormal conditions, particularly in AD, by examining both its beneficial and detrimental effects.

淀粉样蛋白-β的双重性:它在正常状态和阿尔茨海默病状态中的作用。
阿尔茨海默病(AD)是一种神经系统退行性疾病,通过影响脑细胞逐渐损害认知能力、破坏记忆保持并妨碍日常功能。老年痴呆症的一个主要特征是淀粉样蛋白-β(Aβ)斑块的累积,它在疾病进展中起着关键作用。这些斑块引发了一系列事件,包括神经炎症、突触功能障碍、tau 病理学、氧化应激、蛋白质清除受损、线粒体功能障碍和钙平衡紊乱。Aβ 的积累还与注意力缺失症的其他标志性特征密切相关,凸显了其重要性。Aβ 通过淀粉样前体蛋白(APP)的裂解生成,并根据其加工途径发挥双重作用。非淀粉样蛋白生成途径可减少 Aβ 的产生,并具有神经保护和抗炎作用,而淀粉样蛋白生成途径则会导致 Aβ 肽的产生,包括 Aβ40 和 Aβ42,这两种肽会导致 AD 的神经变性和毒性作用。了解Aβ的多方面作用,尤其是在AD中的作用,对于开发针对Aβ代谢、聚集和清除的有效治疗策略,以减轻该疾病的有害后果至关重要。本综述旨在通过研究 Aβ 的有益和有害作用,探讨 Aβ 在正常和异常情况下的机制和功能,尤其是在注意力缺失症中的机制和功能。
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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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