当前位置: X-MOL 学术ACS Chem. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2018-05-21 00:00:00 , DOI: 10.1021/acschemneuro.8b00185
Philip Ryan 1 , Bhautikkumar Patel 1 , Vivek Makwana 1 , Hemant R. Jadhav 2 , Milton Kiefel 3 , Andrew Davey 1, 4, 5 , Tristan A. Reekie 6 , Santosh Rudrawar 1, 4, 5, 6 , Michael Kassiou 6
Affiliation  

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder accounting for 60–80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylation of amyloid-forming proteins, including amyloid precursor protein (APP), tau, and α-synuclein, promotes alternative nonamyloidogenic processing pathways. As such, glycopeptides and related peptidomimetics are being investigated within the AD field. Here we review advancements made in the last 5 years, as well as the arrival of sugar-based derivatives.

中文翻译:

肽,拟肽和糖类碳水化合物结合物可作为阿尔茨海默氏病的淀粉样蛋白聚集抑制剂

阿尔茨海默氏病(AD)是一种进行性神经退行性疾病,占痴呆症病例的60–80%。多年来,AD因果关系归因于淀粉样β(Aβ)聚集物种。最近,针对Aβ聚集的多种疗法在临床试验中失败了,因为在AD和健康患者中发现了Aβ聚集。因此,注意力已经转移到tau蛋白的聚集作为AD的主要驱动力。最近已经开发出许多基于tau蛋白的病理学抑制剂。AD的诊断已从测量晚期老年斑转变为早期生物标志物,淀粉样β和tau单体以及寡聚体。人们正在探索合成肽和某些衍生物结构作为治疗诊断工具,因为它们既具有结合生物标记物的能力,又具有抑制其病理自组装的能力。多项研究表明O-连接的糖苷的添加可以显着改变淀粉样蛋白的聚集动力学。此外,淀粉样蛋白形成蛋白(包括淀粉样蛋白前体蛋白(APP),tau和α-突触核蛋白)的天然O-糖基化促进了其他非淀粉样蛋白生成途径。因此,在AD领域内正在研究糖肽和相关的拟肽。在这里,我们回顾了过去5年中取得的进步以及糖基衍生物的到来。
更新日期:2018-05-21
down
wechat
bug