Design of Novel Hsp90 Inhibitors to Trigger Tau Degradation in Alzheimer’s disease: An Insilico Approach

Kazavali, Shaik (2014) Design of Novel Hsp90 Inhibitors to Trigger Tau Degradation in Alzheimer’s disease: An Insilico Approach. BTech thesis.



Alzheimer’s disease (AD) is one of the most common Protein amyloid-associated Neurodegenerative disorder which is an irreversible and progressive patterns of cognitive and functional impairments. The neuropathological identifications and findings of AD includes presence of plaques and neurofibrillary tangles.Tau hypothesis is a model of neurofibrillary tangles where, hyper phosphorylated tau begins to misfold with other threads of tau. Ultimately, they lead to form neurofibrillary tangles in nerve cells. This involves in the disruption of microtubules, and eventually leads to breaking down of neuron’s passage coordination. This may result in a glitch of biochemical intercommunication between neurons and subsequently leads to death of neurons. Hsp90 is a highly protective molecular chaperone and its functions are stress responses, aids other proteins to fold perfectly, stabilities proteins against heat stress, and helps in protein degradation, and assembly of other vast chaperones for numerous biological purposes. Tau which is a client protein of Hsp90 has been reported to be an important cause of AD. Inhibition of Hsp90, hence has been shown to be a strategy of therapy by directing tau towards degradation pathway. In the present investigation, we have designed novel analogues of geldanamycin, novobiocin as Hsp90 inhibitors and assessed their inhibitory potential. We concluded that analogues-3 of geldanamycin was found to be a better Hsp90-inhibitor than geldanamycin.

Item Type:Thesis (BTech)
Uncontrolled Keywords:Hsp90;Hsp90 inhibitors;tau aggregation;Alzheimer’s disease;Insilico design;Novobiocin;Geldanamycin; Docking;
Subjects:Engineering and Technology > Biomedical Engineering
Divisions: Engineering and Technology > Department of Biotechnology and Medical Engineering
ID Code:6032
Deposited By:Hemanta Biswal
Deposited On:25 Aug 2014 16:56
Last Modified:25 Aug 2014 16:56
Supervisor(s): Paul, S

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