摘要
背景:随着阿尔茨海默病 (AD) 的新生物分子靶标的出现,人们倾向于将它们视为相互排斥和竞争的,最终宣称由于“淀粉样蛋白假说已死”,它需要被完全不同的理论所取代。然而,鉴于错误折叠肽,特别是 β-淀粉样蛋白 (Aβ) 在 AD 发病机制中的作用已得到充分描述,因此需要对 AD 进行广泛的概念化,将不同的理论合并为一个统一的解释,作为一种可行的替代方案.将 AD 的蛋白质聚集机制纳入更广泛的 AD 免疫病模型可以实现这样的目标 - 通过重新定位 Aβ 作为免疫肽的作用可以实现这一目标。结论:本综述提出了 Aβ 是一种免疫肽的概念,AD 是一种自身免疫性疾病,其中 Aβ 是一个关键的分子参与者。作为具有改变免疫功能能力的肽,Aβ是一种免疫肽; Aβ 具有抗菌和免疫调节活性,是一种宿主防御肽; Aβ 具有细胞因子的大部分定义特性,满足细胞因子的广泛定义——原型免疫肽亚型。除了这些免疫活性外,Aβ 还通过坏死和凋亡机制直接和独立地对神经元产生细胞毒性。因此,在大脑暴露于免疫刺激刺激后,先天免疫系统被激活,导致 Aβ 释放为免疫肽(作为宿主防御肽或细胞因子),随后对宿主神经元造成错误的攻击——自身免疫事件。
关键词: 阿尔茨海默病、痴呆、神经炎症、自身免疫、细胞因子、抗菌肽、β-淀粉样蛋白、免疫肽。
Current Alzheimer Research
Title:β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease
Volume: 18 Issue: 11
关键词: 阿尔茨海默病、痴呆、神经炎症、自身免疫、细胞因子、抗菌肽、β-淀粉样蛋白、免疫肽。
摘要:
Background: As new biomolecular targets for Alzheimer’s disease (AD) emerge, there is a tendency to regard these as mutually exclusive and in competition, culminating in declarations that since the “amyloid hypothesis is dead” it needs to be replaced by completely different theories. However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation mechanisms of AD into a more widely-encompassing immunopathic model of AD could accomplish such a goal-a goal which could be achieved by repositioning the role of Aβ as an immunopeptide.
Conclusion: This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities, Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies the broad definition of cytokine-the prototypic immunopeptide subtype. In addition to these immunoactivities, Aβ is also directly and independently cytotoxic to neurons by both necrotic and apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host neurons-an autoimmune event.
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Cite this article as:
β-Amyloid is an Immunopeptide and Alzheimer’s is an Autoimmune Disease, Current Alzheimer Research 2021; 18 (11) . https://dx.doi.org/10.2174/1567205018666211202141650
DOI https://dx.doi.org/10.2174/1567205018666211202141650 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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