Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofib...Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.展开更多
Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8...Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8-HDN)from D.lotus against the PTP1B enzyme.It showed significant inhibitory activity of PTP1B with an IC 50 value of 18.37±0.02μM.A detailed molecular docking study was carried out to analyze the binding orientation,binding energy,and mechanism of inhibition.A comparative investigation of 8-HDN in the catalytic,as well as the allosteric site of PTP1B,was performed.Binding energy data showed that compound 8-HDN is more selective for the allosteric site and hence avoids the problems associated with catalytic site inhibition.The inhibition mechanism of 8-HDN can be further investigated as an active lead compound against PTP1B by using in vitro and in vivo models.展开更多
基金the support by the Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
文摘Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.
基金funded by Higher Education commission,Pakistan(HEC),Grant No.NRPU649.
文摘Proteintyrosine phosphatase 1B(PTP1B)inhibitionis consideredas a potentialtherapeuticfor the treatmentof cancer,type2 diabetes,andobesity.Inour presentwork,weinvestigatedtheanti-diabeticpotentialof8-hydroxydiospyrin(8-HDN)from D.lotus against the PTP1B enzyme.It showed significant inhibitory activity of PTP1B with an IC 50 value of 18.37±0.02μM.A detailed molecular docking study was carried out to analyze the binding orientation,binding energy,and mechanism of inhibition.A comparative investigation of 8-HDN in the catalytic,as well as the allosteric site of PTP1B,was performed.Binding energy data showed that compound 8-HDN is more selective for the allosteric site and hence avoids the problems associated with catalytic site inhibition.The inhibition mechanism of 8-HDN can be further investigated as an active lead compound against PTP1B by using in vitro and in vivo models.
