淀粉样蛋白治疗阿尔茨海默病的方法

Albert J. Robichaud, Ji-In Kim, J. Steven Jacobsen
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摘要

作为公认的最常见的神经退行性疾病,阿尔茨海默病(AD)影响着全球超过1800万人,预计将成为21世纪最大的社会经济负担。阿尔茨海默病的潜在机制尚不清楚,但越来越多的病理生理学证据开始指向两个主要原因,β-淀粉样蛋白斑块和神经原纤维缠结的形成。本综述将涵盖基于淀粉样蛋白假说的疾病修饰方法;也就是说,预防β-淀粉样肽(Aβ)单体的积累、聚集和沉积,首先导致多种寡聚体,然后是原纤维,最终是老年斑,是一种疾病修饰方法的重点。有大量证据表明,这种肽及其随后的聚集与疾病的病因有关,而小分子和生物制药的方法,以防止其积聚已成为许多研究的主题。在过去的十年中,绝大多数的研究一直并将继续集中在这些疾病改善,抗淀粉样变性的方法上。正是这个主题,以及过去和现在通过各种正在探索的代理来改善AD的各种方法,将是本章的重点。关键词:主动免疫;阿尔茨海默病;淀粉样蛋白假说;淀粉样前体蛋白;治疗疾病;fibrillization抑制剂;神经退化;被动免疫;分泌酶
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Approaches to Amyloid Therapies for the Treatment of Alzheimer's Disease
Recognized as the most common of the neurodegenerative disorders, Alzheimer's disease (AD) affects greater than 18 million people worldwide and is predicted to become the largest socioeconomic burden of the twenty-first century. The underlying mechanism of Alzheimer's disease is as yet unknown, but the growing body of pathophysiologic evidence is beginning to point to two main causes, the formation of β-amyloid plaques and neurofibrillary tangles. This review will cover approaches to disease modification that are based on the amyloid hypothesis; that being, the prevention of the accumulation, aggregation, and deposition of β-amyloid peptide (Aβ) monomers, leading first to multiple oligomeric species and then to fibrils and ultimately senile plaques, is the center of focus for an approach to disease modification. There is a wealth of evidence to implicate this peptide and its subsequent aggregation in the etiology of the disease and approaches, both small molecule and biopharmaceutical, to prevent its accumulation have been the subject of much research. The vast majority of this research over the last decade has been, and continues to be, focused on these disease-modifying, antiamyloidogenic approaches to AD. It is this subject, and the various approaches, past and present to amelioration of AD through the various agents being explored, that will be the focus of this chapter. Keywords: active immunization; Alzheimer's disease; amyloid hypothesis; amyloid precursor protein; disease modifying treatments; fibrillization inhibitors; neurodegeneration; passive immunization; secretase
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