Department of Pharmacy
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Item Epigenetic mechanisms in Alzheimer's Disease: Therapeutic potential of Class specific HDAC inhibitors in insulin resistance induced cognitive impairments(JSTAGE, 2018) Taliyan, RajeevNumerous epidemiological studies have demonstrated that insulin resistance contributes to Alzheimer's disease (AD) pathogenesis. However the molecular mechanisms is still remain elusive but various studies have highlighted the epigenetic alterations and involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. In our previous study, we have explored the potential of pan HDAC inhibitor, SAHA, in high fat diet induced insulin resistance. In the present study, we have investigated the potential of isoform specific HDAC inhibitors in insulin resistance induced cognitive impairment in mice. Methods: Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. HFD fed mice were treated with Class I specific HDAC inhibitor, CI-994 or Class II specific HDAC inhibitor, MC-1568 once daily for 2 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured. A battery of behavioural parameters was performed to assess cognitive functions. Results: HFD fed mice exhibit characteristic features of insulin resistance, showed a severe deficit in learning and memory. HFD feeding results in significant increase in Amyloid beta1-42 levels as compared with NPD fed mice In contrast, the mice treated with MC-1568 showed significant improvement in insulin resistance condition, marked decrease in Amyloid beta1-42 and significantly ameliorate the HFD induced decrease in BDNF and CREB level as compared to HFD group. Whereas, the mice treated with Class I HDAC inhibitor, CI-994 failed to show any improvement in insulin resistance and cognitive deficits. Conclusion: Based upon these results, it could be suggested that Class II HDAC inhibitors exert better neuroprotective effects as compared to Class I HDAC inhibitors associated with insulin resistant condition.Item [P2–130]: AR-A014418, A GSK-3β INHIBITOR, ATTENUATES ALZHEIMER'S- LIKE PATHOLOGY IN HIGH FAT DIET-INDUCED COGNITIVE DEFICIT IN MICE(Wiley, 2017-07) Taliyan, RajeevAlzheimer's disease (AD) is characterized by the progressive deposition of fibrillar amyloid-β (Aβ) in the form of extracellular plaques and hyperphosphorylated tau as intraneuronal neuro fibrillary tangles (NFTs). Studies have reported that increased Glycogen synthase kinase-3β (GSK-3β) activity has been associated with hyper phosphorylation of tau. However, the molecular mechanisms of association still remain elusive. Thus, the present study was designed to explore the potential of GSK-3β inhibitor, AR-A014418 in high fat diet (HFD) induced cognitive impairment and AD like pathology.Item Fibroblast Growth Factor 21 and Autophagy Modulation Ameliorates Amyloid β-Induced Alzheimer Disease Pathology in Rats(Wiley, 2021-12) Taliyan, RajeevAlzheimer's disease (AD) is a multifactorial neurodegenerative condition and the most common cause of its initiation is accumulation of oligomeric amyloid beta1-42 (Aβ1-42). In recent past, several studies have shown autophagy deficits in AD may resulted accumulation of misfolded protein, Aβ1-42 and phosphorylated tau (ptau). Fibroblast growth factor 21 (FGF21), a metabolic hormone, has shown strong neuroprotective efficacy via increasing autophagic flux in AD. Therefore, this study was designed to investigate the synergistic neuroprotective efficacy of lentiviral FGF21 gene (LV-FGF21) delivery and rapamycin-autophagy modulator in Aβ1-42 induced AD in rats.