In Silico Homology Modeling of Presenilin 2-Therapeutic Target for Alzheimer's disease

Abstract

Alzheimer’s disease is a neurodegenerative disorder which is caused by several mutations in causative proteins like Amyloid Precursor Protein (APP), Presenilin1 (PSEN1), and Presenilin2 (PSEN2). Mutations in presenilin 2 lead to the overproduction of amyloid beta peptide which gets accumulated in the brain and causes neuron death. This result in Early Onset Alzheimer’s disease (EOAD) and there are around 17 mutations in presenilin 2 results in this disease condition. There are 3 isoforms of PSEN2 which are normally found in the cells. Three dimensional structure of presenilin 2 has not been determined; hence, in this study the structure of presenilin 2 was predicted using homology modeling. The 3dimensional structures are modeled using Modeller9.20, Swiss Model and Geno3D. The structures are validated using PROCHECK. The structure of Swiss Model was found to be more reliable with fewer amino acids in the disallowed region, followed by Modeller9.0 and Geno3D. These structures will be fundamental in determining the crystal structure of presenilin 2 and for drug discovery.