PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a prevalent neurodegenerative disorder characterized by abnormal protein deposition. With an alarming 30 million people affected worldwide, AD poses a significant public health concern. While inhibiting key enzymes such as β-site amyloid precursor protein-cleaving enzyme 1 and γ-secretase or enhancing amyloid-β clearance, has been considered the reasonable strategy for AD treatment, their efficacy has been compromised by ineffectiveness. Furthermore, our understanding of AD pathogenesis remains incomplete. Normal aging is associated with a decline in glucose uptake in the brain, a process exacerbated in patients with AD, leading to significant impairment of a critical post-translational modification: glycosylation. Glycosylation, a finely regulated mechanism of intracellular secondary protein processing, plays a pivotal role in regulating essential functions such as synaptogenesis, neurogenesis, axon guidance, as well as learning and memory within the central nervous system. Advanced glycomic analysis has unveiled that abnormal glycosylation of key AD-related proteins closely correlates with the onset and progression of the disease. In this context, we aimed to delve into the intricate role and underlying mechanisms of glycosylation in the etiopathology and pathogenesis of AD. By highlighting the potential of targeting glycosylation as a promising and alternative therapeutic avenue for managing AD, we strive to contribute to the advancement of treatment strategies for this debilitating condition.
摘要：
阿尔茨海默病(Alzheimer’sdisease,AD)是一种以蛋白质沉积异常为特征的神经退行性疾病。全球有惊人的3000万人受到影响，AD引起了重大的公共卫生问题。在抑制关键酶如β-位点淀粉样前体蛋白裂解酶1和γ-分泌酶或增强淀粉样蛋白-β清除的同时,一直被认为是治疗AD的合理策略，它们的功效因无效而受到损害。此外，我们对AD发病机制的理解仍不完全.正常衰老与大脑中葡萄糖摄取的下降有关，一个在AD患者中加剧的过程，导致关键翻译后修饰的显着损害：糖基化。糖基化,细胞内次级蛋白质加工的精细调节机制，在调节重要功能，如突触发生，神经发生，轴突引导,以及中枢神经系统的学习和记忆。高级糖组学分析揭示了关键AD相关蛋白的异常糖基化与疾病的发作和进展密切相关。在这种情况下，我们旨在深入研究糖基化在AD的病因和发病机制中的复杂作用和潜在机制。通过强调靶向糖基化作为治疗AD的有希望和替代治疗途径的潜力，我们努力为这种衰弱状态的治疗策略的发展做出贡献.
