| dc.description.abstract | Alzheimer's disease (AD) is the most common irreversible dementia, caused by accumulation of protein aggregates in the central nervous system, with symptoms that include memory loss and behavioural abnormalities. Cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartate receptor (NMDAR) antagonists are current treatment options for mild to moderate AD. These agents are not used to cure the illness, but rather as symptomatic therapy. Heat Shock Protein (HSP90), is one of the molecular chaperones that plays a role in AD pathogenesis. HSP90’s main function is to regulate the heat shock factor-1 (HSF-1) transcription factor, which is the key regulator of the heat shock response. Inhibition of HSP90 activates HSF-1 and the subsequent induction of heat shock proteins such as HSP70, HSP40 and HSP27. Such protein assist the folding of newly synthesized or misfolded proteins, preventing their aggregation. Therefore, HSP90 inhibitors protect against protein toxicity and reduces brain aggregate to form in AD. The HSP90 protein crystal structure (PDB ID; 2bz5) was used to dock a diverse structural database of about 12 000 amine containing compounds from the Maybridge Screening Collection using Fast Rigid Exhaustive Docking (FRED). The top five hundred-docked compounds were viewed using Visualization & Communication of Modeling Results (VIDA), and the top 50 compounds were analysed for important binding interactions and low Chemgausse4 scores. Ten of these compounds were selected based on their interaction profile with the desired HSP90 active site amino acids. Thereafter, the ten MayBridge compounds were drawn on Sigma-Aldrich and searched for structures that show at least 70% similarity, to the selected MayBridge compounds. | en_US |
