Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Int J Mol Sci. 2021 Dec 29;23(1):345. doi: 10.3390/ijms23010345.
Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and the formation of neurofibrillary tangles (NTFs), as well as neuronal dysfunctions in the brain, but in fact, patients have shown a sustained disease progression for at least 10 to 15 years before these pathologic biomarkers can be detected. Consequently, as the most common chronic neurological disease in the elderly, the challenge of AD treatment is that it is short of effective biomarkers for early diagnosis. The protein quality control system is a collection of cellular pathways that can recognize damaged proteins and thereby modulate their turnover. Abundant evidence indicates that the accumulation of abnormal proteins in AD is closely related to the dysfunction of the protein quality control system. In particular, it is the synthesis, degradation, and removal of essential biological components that have already changed in the early stage of AD, which further encourages us to pay more attention to the protein quality control system. The review mainly focuses on the endoplasmic reticulum system (ERS), autophagy-lysosome system (ALS) and the ubiquitin-proteasome system (UPS), and deeply discusses the relationship between the protein quality control system and the abnormal proteins of AD, which can not only help us to understand how and why the complex regulatory system becomes malfunctional during AD progression, but also provide more novel therapeutic strategies to prevent the development of AD.
阿尔茨海默病（AD）的特征是老年斑（SPs）的沉积和神经原纤维缠结（NTFs）的形成，以及大脑神经元功能障碍，但实际上，在这些病理生物标志物被检测到之前，患者已经表现出持续的疾病进展至少 10 到 15 年。因此，作为老年人最常见的慢性神经退行性疾病，AD 治疗的挑战在于缺乏有效的早期诊断生物标志物。蛋白质质量控制系统是一组可以识别受损蛋白质的细胞途径，从而调节其周转率。大量证据表明，AD 中异常蛋白质的积累与蛋白质质量控制系统的功能障碍密切相关。特别是在 AD 的早期阶段，已经改变了必需生物成分的合成、降解和去除，这进一步促使我们更加关注蛋白质质量控制系统。该综述主要集中在内质网系统（ERS）、自噬溶酶体系统（ALS）和泛素-蛋白酶体系统（UPS），并深入探讨了蛋白质质量控制系统与 AD 异常蛋白质之间的关系，这不仅有助于我们了解在 AD 进展过程中，复杂的调节系统是如何以及为何变得功能失调的，而且为预防 AD 的发展提供了更具创新性的治疗策略。
