Speaker at Pharmaceutics and Drug Delivery Systems 2022 - Violina Kakoty
Birla Institute of Technology and Science-Pilani, India
Title : Insulin Resistance Associated Alzheimer Disease Condition in Rats is ameliorated via Epigenetic Regulation and Autophagy Modulation


Insulin resistance (IR) and accumulation of amyloid beta (Aβ) oligomers are potential causative factor for Alzheimer 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 (20μM) and vori (4μM) 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 protein2 (MAP2). In order to develop IR condition, rats were fed a high fat diet (HFD) for 8weeks and then subjected to intracerebroventricular Aβ1-42 administration. Subsequently, their treatment was initiated with rapa (1mg/kg, i.p.) and vori (50mg/kg, i.p.) once daily for 28days. 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.


Violina Kakoty’s area of interest is to explore the neuroprotective potential of autophagy and epigenetic modulators in ameliorating the pathological cascade of metabolic syndrome associated/and neurodegenerative disorders such as Alzheimer and Parkinson disease. Further, she has had the opportunity of moving to Taipei Medical University, Taipei, Taiwan for a period of 6 months for attaining training and completing a part of her research work related to the development of lentivirus production and its use to mitigate Alzheimer and Parkinson disease condition. She has
been awarded with many prestigious awards like University rank holder (gold medalist) during Masters in Pharmacy from Shoolini University, best oral presentation Award at Young Pharmacologist Symposium jointly organized by National Institute of Pharmaceutical Education and Research Raebareli (NIPER-R) and Indian Pharmacological society (IPS). She has also published review and research papers in peer reviewed international journals and delivered presentations in conferences of international and national repute.