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In Silico Analysis of Mutations Along the Amyloidogenic Pathway in Alzheimer’s Disease


  • Wenqi Zhao Cambridge University Centre of Misfolding Diseases



Through in silico simulation of mutations and their effect on protein structure, we conclusively examine the impact of mutations along the amyloidogenic pathway in three steps: as factors which undermine the suppression of A? production from BACE-1; the inhibition of amyloid breakdown by neprilysin; and the aggregation of A? monomers through oligomeric and fibril stages. We verified the significance of mutations in miRNA that particularly complement with BACE1. We discovered novel mutations that impede most significantly on neprilysin function. And we examined the importance of mutations on the propensity of A? to aggregate. The results are significant: the framework and algorithm of the paper can be employed to make accurate predictions for patients from simple and widely accessible genetic data. Beyond that, given the ubiquity of proteins within our body, the functions for modelling miRNA suppression, predicting protein function and calculating protein aggregation also have widespread uses in all areas of human biology and medicine.


Mutation, A-beta, Aggregation


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