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Rapidly Progressive Alzheimer's disease (rpAD) is a disease characterized by rapid cognitive
loss. It progresses quickly over the course of weeks to months and sometimes may take up to
two to three years. It’s rare and difficult to diagnose although accurate diagnosis is extremely
crucial for its treatment. Recent evidence suggests Tau as a promising therapeutic agent for the
development of disease-modifying drugsfor rpAD due to the involvement of Tau abnormalities
in rpAD neurodegeneration. To determine whether Tau is a suitable therapeutic target, in silico
tools were used to analyse the interaction of proteins isolated by Tau IP. It is identified that
proteins interact with MAPT during the pathology of disease and play a role in progression of
rpAD. The specific interaction between the MAPT region belonging from the MTB domain
2MZ7 and its interactors Neuromodulin, Synaptophysin and RhoA were investigated using
molecular docking and visualization tools like PyRx, PyMOL, Discovery Studio, and LigPlot+
and binding energies and bonding between the amino acids was observed and evaluated.
Protein network analysis revealed an aberration towards apoptotic pathway and signaling
pathway. Furthermore, binding of different drug compounds including Methamphetamine,
Ascorbic acid and Doxorubicin were evaluated through docking in silico. Doxorubicin showed
the highest binding energy of -6.0 kcal/mol with 2MZ7. These drug compounds and their
interaction with 2MZ7 yielding high binding affinity shows that binding site of MAPT can be
blocked using Doxorubicin to prevent the interaction of pathological proteins that are involved
in the accelerated progression of rpAD.