Bioinformatics characterization of mutations in the protein presenilin-1, presenilin-2 and Amyloid protein precursor in relation with Familiar Alzheimer disease

Abstract

Introduction: Alzheimer's disease is manifested as neuronal death due to damage to the nervous tissue and whose neuropathological hallmarks are protein deposits such as amyloid plaques and neurofibrillary tangles. Objective: To relate the clinical reported for Familial Alzheimer's disease and the changes of 10 selected mutations in the susceptible regions, to understand the effect on the protein structure from the bioinformatics characterization. Methodology: The information was compiled from the Alzforum, Pubmed, Uniprot and Embl databases. The mutation susceptibility analysis is done with the Rostlab SNAP2 software and the post-translational modifications are made with the Swiss-ExPASY tool. Results: A frequency table oriented to clinical cases associated with missense mutations that cause Alzheimer's disease was established and the frequency of amino acid changes was found and compared with the composition of amino acids present for PS1, with a percentage of 12% for Leu, in PS2 with Leu at 12.9% and for the carboxy terminal fragment of 99 amino acids of APP with a value of 13.1% for Val. Discussion and conclusion: The amino acids produces changes based on their chemical characteristics, the nonpolar amino acids were more frequent and it is due to the high proportion of protein structure located in the neuronal membrane. The susceptibility analysis complements the effect of the change for the 20 amino acids in the protein structure, guided by the polarity changes.