The amyloid hypothesis of Alzheimer's disease (AD) maintains that the accumulation of the amyloid β protein (Aβ) is a critical event in disease pathogenesis. Conformational changes of Aβ peptide result in its transformation from native monomeric state to the toxic soluble dimers, oligomers and insoluble aggregates that are hallmarks of Alzheimer’s disease (AD). Interactions of zinc ions with Aβ are mediated by the N-terminal Aβ1–16 domain and appear to play a key role in AD progression. There is a range of results indicating that these interactions trigger the Aβ plaque formation. Dr. Istrate and co-authors have found that variants zinc-induced oligomerization of Aβ is governed by conformational changes in the minimal zinc binding site 6HDSGYEVHH14 [Istrate, Andrey N., et al. "Interplay of histidine residues of the Alzheimer’s disease Aβ peptide governs its Zn-induced oligomerization." Scientific reports 6 (2016).]. It is now clear that residue H6 and segment 11EVHH14, which are part of this site can be considered as promising targets for rational design of the AD-modifying drugs aimed at blocking pathological Aβ aggregation.
Our company suggests development of the compounds, which will affect zinc binding site of amyloid β protein in human cells. We suggest multi-step strategy, involving virtual screening, high-throughput screening, in silico drug design, ADME/Tox and pharmacokinetics optimization and other preclinical development of clinical trials candidate compounds. If you choose our investment project, you will be able to get income of 1 - 2 mln. usd. (estimated cost of clinical trials candidate) in around 2-3 years of preclinical drug development.