Discovery of Dual Aβ/Tau Inhibitors and Evaluation of Their Therapeutic Effect on a
aggregation inhibitors
bivalent ligands
multitarget-directed ligands
protein aggregates
tau protein
β-amyloid
Journal
ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337
Informations de publication
Date de publication:
07 12 2022
07 12 2022
Historique:
pubmed:
30
11
2022
medline:
15
12
2022
entrez:
29
11
2022
Statut:
ppublish
Résumé
Alzheimer's disease (AD), the most common type of dementia, currently represents an extremely challenging and unmet medical need worldwide. Amyloid-β (Aβ) and Tau proteins are prototypical AD hallmarks, as well as validated drug targets. Accumulating evidence now suggests that they synergistically contribute to disease pathogenesis. This could not only help explain negative results from anti-Aβ clinical trials but also indicate that therapies solely directed at one of them may have to be reconsidered. Based on this, herein, we describe the development of a focused library of 2,4-thiazolidinedione (TZD)-based bivalent derivatives as dual Aβ and Tau aggregation inhibitors. The aggregating activity of the 24 synthesized derivatives was tested in intact
Identifiants
pubmed: 36445009
doi: 10.1021/acschemneuro.2c00357
pmc: PMC9732823
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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