IN-SILICO ANALYSIS OF POTENTIAL TAU PROTEIN KINASE INHIBITORS USING DOCKING STUDIES FOR THE TREATMENT OF ALZHEIMER'S DISEASE

Abstract

Alzheimer’s disease is a brain disorder which leads to serious deterioration in many mental functions like memory, orientation, language and judgment. The main characteristic feature of this disease is the formation of senile plaques (mostly β amyloid) and neurofibrillary tangles (formed due to altered tau protein) which results in neuronal destructions. Neurofibrillary tangles are formed due to hyperphosphorylation of tau and its subsequent aggregation. Several kinases are responsible for phosphorylation of tau protein, but in AD brains these kinases are upregulated. Inhibition of multiple kinases may prevent tau aggregation in neurofibrilary tangles and prevent progress of Alzheimer’s and its associated neurodegeneration. In this study we targeted GSK3β and CDK5/p25 which play the most prominent role in hyperphosphorylation of tau. Plant derivatives especially flavonoids are suitable candidates for inhibitors as they are nontoxic and possess anti-oxidant properties. Several plant derivatives were selected and autodock4.2 was used to analyse their inhibition potential for GSK3β and CDK5. Flavonoids showing minimum binding energy can be used as potential inhibitors in therapy against Alzheimer’s.