Role of glycosphingolipids and therapeutic perspectives on Alzheimer's disease
Role of glycosphingolipids and therapeutic perspectives on Alzheimer's disease
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DOI：
10.2174/187152706777950710
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发表时间：
2006-08-01
影响因子：
3
通讯作者：
Yamamoto, Hiroko
中科院分区：
文献类型：
--
作者：
Mutoh, Tatsuro;Hirabayashi, Yoshio;Yamamoto, Hiroko
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，分为两种形式：早发家族性和晚发散发性形式。早发型遗传病例（家族性 AD (FAD)）约占所有 AD 病例的 10%。迄今为止，高度原纤维化和病理性Aβ肽形成被认为是这种疾病的基本分子基础。然而，最近为找出发病机制所做的巨大努力表明，这种疾病有多种原因，例如鞘糖脂异常、神经营养蛋白信号传导受损、蛋白质运输和蛋白质周转。其中大部分方面是由 FAD 相关早老素的研究揭示的。在这篇综述中，我们将重点关注细胞脂质许多异常方面的当前知识，尤其是糖鞘脂，而不是由突变早老素作为模型系统引起的致病性 Aβ 产生。此外，我们将讨论这些鞘糖脂异常如何导致这种疾病的病理状况。
Alzheimer's disease (AD) is a devastating neurodegenerative disorder dividing into two forms, early onset familial and late onset sporadic forms. Early onset genetic cases (familial AD (FAD)) constitute about 10% of all AD cases. Heretofore, highly fibrillinogenic and pathological A beta peptide formation is regarded as the fundamental molecular basis for this disorder. Recent enormous efforts to find out a pathogenesis, however, have revealed that this disorder has a multiplicity of causes such as glycosphingolipids abnormalities, impairment of neurotrophin signaling, protein trafficking, and protein turnover. Most of these aspects were disclosed by the studies on FAD-related presenilin. In this review, we will focus on the current knowledge of many abnormal aspects of cellular lipids, especially glycosphingolipids other than a pathogenic A beta production caused by the mutant presenilins as a model system. Moreover, we will discuss how these glycosphingolipids abnormalities cause the pathological conditions found in this disorder.