Department of Pharmacy

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Author: search.filters.author.Marathe, SandhyaSubject: search.filters.subject.Alzheimer’s disease (AD)

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    Epigenetic regulation and autophagy modulation debilitates insulin resistance associated Alzheimer’s disease condition in rats
    (Springer, 2022-01) Taliyan, Rajeev; Marathe, Sandhya
    Insulin resistance (IR) and accumulation of amyloid beta (Aβ) oligomers are potential causative factor for Alzheimer’s Disease (AD). Simultaneously, enhanced clearance level of these oligomers through autophagy activation bring novel insights into their therapeutic paradigm. Autophagy activation is negatively correlated with mammalian target of rapamycin (mTOR) and dysregulated mTOR level due to epigenetic alterations can further culminate towards AD pathogenesis. Therefore, in the current study we explored the neuroprotective efficacy of rapamycin (rapa) and vorinostat (vori) in-vitro and in-vivo. Aβ1–42 treated SH-SY5Y cells were exposed to rapa (20 μM) and vori (4 μM) to analyse mRNA expression of amyloid precursor protein (APP), brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), neuronal growth factor (NGF), beclin-1, microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate (LC3), lysosome-associated membrane protein 2 (LAMP2) and microtubule associated protein 2 (MAP2). In order to develop IR condition, rats were fed a high fat diet (HFD) for 8 weeks and then subjected to intracerebroventricular Aβ1–42 administration. Subsequently, their treatment was initiated with rapa (1 mg/kg, i.p.) and vori (50 mg/kg, i.p.) once daily for 28 days. Morris water maze was performed to govern cognitive impairment followed by sacrification for subsequent mRNA, biochemical, western blot and histological estimations. For all the measured parameters, a significant improvement was observed amongst the combination treatment group in contrast to that of the HFD + Aβ1–42 group and that of the groups treated with the drugs alone. Outcomes of the present study thus suggest that combination therapy with rapa and vori provide a prospective therapeutic approach to ameliorate AD symptoms exacerbated by IR.
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    Exploring the Neuroprotective Potential of Rosiglitazone Embedded Nanocarrier System on Streptozotocin Induced Mice Model of Alzheimer’s Disease
    (Springer, 2020-07) Taliyan, Rajeev; Chitkara, Deepak; Marathe, Sandhya
    Alzheimer’s disease (AD) is a neurodegenerative disorder imposing great threat to an individual’s cognitive capability. Mounting evidence suggests that type 2 diabetes mellitus (T2DM) and AD is closely associated with impaired insulin signalling and glucose metabolism in the brain. Member of the peroxisome proliferator-activated receptor (PPAR) family, especially PPARγ agonists, has been well known for their insulin-sensitizing actions, but due to low water solubility, poor penetration into the brain and associated toxicity limit their use clinically. Therefore, this study has been undertaken to investigate the neuroprotective potential of rosiglitazone embedded nanocarrier system on streptozotocin (STZ) induced mice model of AD. In vitro neuroprotective efficacy of rosiglitazone was determined on SH-SY5Y cells by assessing the messenger ribonulceic acid (mRNA) expression level of genes implicated for cognitive function. AD in mice was developed by intracerebroventricular (ICV) administration of STZ (3 mg/kg) directly into the lateral ventricles of the mice brain. The cognitive parameters and mRNA expression levels were evaluated after treatment with the free form of rosiglitazone as well as its nano-formulated form. It was observed that rosiglitazone elicits neuroprotection on SH-SY5Y cells as evidenced from the upregulation of genes such as cyclic-AMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and nerve growth factor (NGF), which are involved in cognitive functions. Further, the nano-formulated rosiglitazone induced better neuroprotective efficacy than its free drug treatment on animal model of AD as evidenced by attenuating the behavioural and cognitive abnormalities, oxido-nitrosative stress and pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6a) along with improved antioxidant enzymes (superoxide dismutase (SOD), reduced glutathione (GSH), acetylcholine, neuronal density and expression of CREB, BDNF, GDNF and NGF in the hippocampal region. Based on the results, it can be concluded that rosiglitazone nanoformulation exerts strong neuroprotection via increasing the mRNA expression of growth factors and inhibition of oxidative stress, and neuroinflammation eventually prevents neuronal injury in AD