Molecular basis of Alzheimer Disease (DCM.AD007.152)

Area tematica

Scienze chimiche e tecnologie dei materiali

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC)

Responsabile di progetto

SIMONA TOMASELLI
Telefono: 0223699722
E-mail: simona.tomaselli@scitec.cnr.it

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease affecting about 45 million people worldwide and is typified by memory loss, synaptic and cognitive dysfunction. Central to the development of AD is the self-association of the ²-amyloid (Ab) peptide, which can form soluble oligomers, the main neurotoxic species, and fibrils. The inhibition of Ab aggregation, the most widely recognized culprit of AD, has been considered a primary therapeutic strategy for its treatment. Thousands of molecules have been screened to identify new substances that can control the formation of A² aggregates. Natural polyphenols emerged as the most promising.
Both synthetic and natural compounds will be tested for the capability to interfere with the oligomerisation of different A² peptides (A²40, A²42, A²pE3-42), normally present in AD brains and having a different assembly pathway.
Solution NMR and molecular docking studies will clarify the molecular basis of their ability to interfere with the first steps of the oligomerization and identify the steric and chemical requirements necessary for an effective drug. Molecular data will be complemented by in vitro and in vivo studies.

Obiettivi

Identification of Ab peptide aggregation inhibitors
Description of the molecular mechanism of action of inhibitors

Data inizio attività

01/07/2020

Parole chiave

NMR, amyloid, aggregation inhibitors

Ultimo aggiornamento: 03/01/2025