期刊
ACS CHEMICAL NEUROSCIENCE
卷 9, 期 7, 页码 1530-1551出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.8b00185
关键词
Beta-amyloid; tau; Alzheimer's disease; neurodegenerative disease; peptidomimetics; glycopeptides; aggregation inhibitors; GlcNAc; glycosylation
资金
- Australian Research Council - Discovery Early Career Research Award [ARC DECRA: DE140101632]
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-beta (A beta) aggregated species. Recently, multiple therapies that target A beta aggregation have failed in clinical trials, since A beta 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-beta 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 alpha-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.
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