Alzheimer’s disease (AD) is the most common neurodegenerative disease, related with neuropathological hallmarks such as amyloid plaques in the brain of old-aged individuals. Although the major insoluble component of amyloid plaques has been identified as the accumulated Aβ peptide, literature data indicate that the molecular composition of plaques is complex and consists of many other, still poorly studied,peptides or proteins. Rational drug design targeting Aβ accumulation is the latest trend in the field of protein aggregation research, since current strategies or practices, aiming at addressing Alzheimer’s complex challenges, have not achieved the wanted results.
This study is a multidisciplinary project on the development of small molecules efficient to inhibit Αβ accumulation, the triggering event for AD progression. Potent inhibitors can be either a) short protein segments, derived from polypeptide chains and ideally designed to interact with protein-targets, or b) natural products, originating from natural sources, that prominently modulate amyloid formation. The afore mentioned molecules interfere with the process of amyloid formation occurring in AD and can be powerful candidates against AD pathogenesis.
The basic idea behind the project is to answer open and challenging questions on the Alzheimer therapeutics field by combining experimental and bioinformatics analyses in order to design inhibitors of Aβ accumulation and propose the most promising molecules as potent “anti-Aβ” drugs. Our goal is to extensively study the properties of all potent inhibitors, utilizing an in vivo, in vitro and in silico workflow. In the proposed study, we intend (a) to design exhaustively potent inhibitors of Αβ, with the aid of literature and an in silico methodology, (b) to synthesize, produce and purify these molecules with classical organic chemistry methods, (c) to theoretically and experimentally investigate the inhibition properties of molecules by performing multiple aggregation assays, (d) to screen their functional properties on C. elegans AD models and (e) to test cytotoxic attributes of the most promising molecules into properly selected cell line cultures. The above process will lead to (f) patents for the most promising molecules, expected to act as dynamic and innovative drugs for the AD.
Briefly, our proposed study is a realistic collaboration between academia (Section of Cell Biology & Biophysics-NKUA, Laboratory of Pharmacognosy and Chemistry of Natural Products-UoP, Institute of Biology, Medicinal Chemistry & Biotechnology-NHRF) and industry (BODERM SA, BioAssist SA) that (a) is anticipated to give prominence to novel “Anti-Αβ” molecules, eligible for inhibiting or eliminating unpleasant accumulation in patients suffering from AD and (b) is expected to bring together organizations both from academia and industry in a common, ambitious and, perhaps, very profitable, in the long run, project; the development and production of a powerful, potential drug against AD.