Peptides, Peptidomimetics, and Carbohydrate-Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer's Disease

ACS Chemical Neuroscience
Philip RyanMichael Kassiou

Abstract

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 investigate...Continue Reading

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Citations

Sep 19, 2019·Journal of Biomolecular Structure & Dynamics·Simranjeet Singh NarangBhupesh Goyal
Apr 1, 2020·Journal of Molecular Recognition : JMR·Elena Moreno-CastilloPedro A Valiente
Jan 19, 2021·ACS Chemical Neuroscience·Elena LenciAndrea Trabocchi
Feb 4, 2021·ACS Chemical Neuroscience·Yehong GongQingwen Zhang
Feb 27, 2020·Chemical Reviews·Moran Frenkel-PinterLuke J Leman
Mar 2, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kyung-Won ParkJoanna L Jankowsky
Apr 13, 2021·ACS Chemical Neuroscience·Grazia Maria Letizia ConsoliGiuseppe Pappalardo
May 18, 2021·ACS Applied Materials & Interfaces·Lin ZhuLinqi Shi
Jun 1, 2021·ACS Omega·Nalini V GorantlaSubashchandrabose Chinnathambi
Jun 20, 2020·ACS Chemical Neuroscience·Philip RyanSantosh Rudrawar
Apr 16, 2019·ACS Chemical Neuroscience·Philip RyanSantosh Rudrawar

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