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

    Author(s)
    Ryan, Philip
    Patel, Bhautikkumar
    Makwana, Vivek
    Jadhav, Hemant R
    Kiefel, Milton
    Davey, Andrew
    Reekie, Tristan A
    Rudrawar, Santosh
    Kassiou, Michael
    Griffith University Author(s)
    Kiefel, Milton
    Rudrawar, Santosh
    Davey, Andrew
    Year published
    2018
    Metadata
    Show full item record
    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 ...
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    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.
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    Journal Title
    ACS Chemical Neuroscience
    Volume
    9
    Issue
    7
    DOI
    https://doi.org/10.1021/acschemneuro.8b00185
    Subject
    Medicinal and biomolecular chemistry
    Medicinal and biomolecular chemistry not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/381651
    Collection
    • Journal articles

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