Histone Deacetylase 6 as A Putative Target in Alzheimer’s Disease Therapeutics

Degeneration or loss of brain cells called neurons results in several neurodegenerative disorders (NDDs) and currently, millions of people across the world are suffering from them. The increase in the occurrence of these age-related disorders is witnessed majorly due to lifestyle changes. NDDs harm the overall functioning of the body which can also be fatal to life. Alzheimer’s Disease (AD) is the most prevalent in the list of NDDs which affects the memory of patients. Oxidative stress performs a wide role in AD pathology and along with that several proteins and enzymes are responsible for the occurrence of AD. One of them is Histone Deacetylase6 (HDAC6). Normally it is responsible for the release of neurotransmitters but in the diseased condition, it becomes abundant in the nucleus which hinders the function and mechanisms and results in dysfunction of the brain. The deteriorated health of the brain leads to AD. This study, utilizing computational-based molecular docking, presents the binding of multiple types of FDA-approved drugs (Anticancer, Antihypertension, Antidiabetic) with the protein for inhibition. To reduce the activity of HDAC6 as a potential therapy for AD, the AutoDock vina-1.5.7 tool was utilized for virtual screening and prediction of the binding affinity of drugs. Following a simulated screening of several different compounds, it was observed that Bicalutamide had the highest binding affinity, measuring -9 kcal/mol. Bicalutamide is an anticancer drug that may be put through additional pre-clinical and clinical testing to produce medications that are repurposed for the treatment of chronic diseases like AD.