Yin Rui-Hua, Tan Lan, Jiang Teng, Yu Jin-Tai
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao, Shandong Province 266071, China.
Curr Alzheimer Res. 2014;11(8):755-64. doi: 10.2174/156720501108140910121425.
The misfolding and aggregation of specific proteins within nervous system occur in most age-associated neurodegenerative diseases including Alzheimer's disease (AD). This kind of disorders have been classified as the protein misfolding disease or proteopathy which share key biophysical and biochemical characteristics with prion diseases. In AD, β-amyloid (Aβ) and tau protein, capital agents for the senile plaques and intracellular neurofibrillary tangles, are called 'prionoids' indicating that proteins exhibit prion-like properties. In this review, we describe the prion-like mechanisms in the progression that the Aβ and tau are induced to misfold and self-assemble by a process of templated conformational change and then the lesion caused by the pathogenic agents spread out through the cell-to-cell transportation, including release of intracellular seeds by the donor cell, cellular uptake by the recipient and intercellular transport. This hypothesis will suggest new therapeutic strategies for AD, especially valuable in the pre-symptomatic phase.
特定蛋白质在神经系统中的错误折叠和聚集发生在大多数与年龄相关的神经退行性疾病中,包括阿尔茨海默病(AD)。这类疾病已被归类为蛋白质错误折叠疾病或蛋白病,它们与朊病毒疾病具有关键的生物物理和生化特征。在AD中,β-淀粉样蛋白(Aβ)和tau蛋白是老年斑和细胞内神经原纤维缠结的主要成分,被称为“类朊病毒”,表明这些蛋白质具有类似朊病毒的特性。在这篇综述中,我们描述了Aβ和tau在疾病进展过程中通过模板化构象变化过程被诱导错误折叠和自组装的类朊病毒机制,然后致病因子引起的损伤通过细胞间运输扩散,包括供体细胞释放细胞内种子、受体细胞的细胞摄取和细胞间转运。这一假说将为AD提出新的治疗策略,在症状前阶段尤其有价值。