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

Thematic area

Chemical sciences and materials technology

Project area

Structure responsible for the research project

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

Project manager

SIMONA TOMASELLI
Phone number: 0223699722
Email: 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.

Goals

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

Start date of activity

01/07/2020

Keywords

NMR, amyloid, aggregation inhibitors

Last update: 03/01/2025