Identification of potential anti-BACE1 drug molecules for Alzheimer’s dementia utilizing in- silico approaches



Authors:Meenu Narwal1, Sunil2, Simantini Ghosh*3


Institute for Empowerment by Arts Science and Technology, Sonepat, Haryana 1310011

Shiv Nadar University, Grater Noida, Uttar Pradesh 2013142

Ashoka University, Sonepat, Haryana 1310013


Corresponding Author*: Dr.Simantini Ghosh, Assistant Professor, Department of Psychology, Ashoka University, Haryana, India. Phone: +91-1302300064, Email: simi@ashoka.edu.in


Alzheimer disease (AD) is a neurodegenerative diseasethat leads to an irreversible loss of neurons and dysfunction of neurovascular system, which together contribute to a gradual loss in memory. Alzheimer’s dementia has been characterised by deposition and aggregation of β-amyloid peptides in the brain and cerebral blood vessels. Several lines of evidence indicate that localized disruption of the blood-brain barrier may precede, accelerate, or contribute to neuronal dysfunction and thus, AD. A significant rise in cases of AD has been observed throughout the world, however, no therapy has yet been successful in curing the diseases. Several potential drug targets for AD has been identified, and among them beta-site amyloid precursor protein cleaving enzyme (BACE1), an aspartic protease, is a prominent target for drug discovery. BACE1 is responsible for generation of β-amyloid peptides. However, most of BACE1 inhibitors are known to have cytotoxicity and poor bioavailability in the brain due to the extremely restrictive nature of blood-brain barrier. Involvement of multiple receptors and proteins into the AD pathogenesis, necessitates the identification of multi-target drug entities. Thus, designing a multi-target novel inhibitor of BACE1 with reduced cytotoxicity and increased permeability through blood-brain barrier could be a promising strategy for the treatment of AD. The current study explores the in-silico multi-target binding pattern of potential drug entities against BACE1 and further with other target proteins responsible for the pathogenesis of AD. Utilizing bioinformatics approaches, such as molecular docking, we have identified anti-BACE1 molecules that can be studied further as potential therapies. These drugs will be tested further for the toxicity, blood-brain permeability and neuroprotection in the cell-culture and animal models of Alzheimer’s disease.