Day2

  • Cairo University, Egypt.
  • Title:A DPP-1 Inhibitor Ameliorates Neurodegeneration in Aluminium Chloride Induced Alzheimer’s Disease Rats via Acting on Klotho, AKT/ERK and JAK/STAT Signalling Pathways.
  • Time :

Abstract:
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders contributing the majority of dementia cases worldwide. The main pathologic hallmarks of AD are senile plaques (SP) and neurofibrillary tangles (NFT) in addition to several molecular factors like neuroinflammation and increased oxidative. Klotho is an antiaging protein expressed by hippocampal neurons and plays a strikingly antioxidant, anti-inflammatory role. Klotho deficiency has been associated with hippocampal neurodegeneration and memory deficits together with elevated oxidative stress. Gliptins have been shown to dampen neurodegeneration via modulating glucagon-like peptide (GLP)-1. This peptide, acting on GLP-1R in the brain, exerts central anti-inflammatory and antiapoptotic effects. We have previously reported the neuroprotective effects of vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in two different models of dementia and cognitive decline induced by high fat high fructose alone or with aluminium chloride (AlCl3) administration via enhancing klotho expression and activating its downstream signaling pathways. In the present study, we investigated the favorable effects of vildagliptin in a rat model of AD induced by AlCl3 oral administration alone (100 mg/kg/day) for 60 days. Rats were orally treated with Vildagliptin (10 mg/kg) for 60 days along with AlCl3 administration. Vildagliptin treatment enhanced general activities together with spatial memory and learning in open field test and morris water maze (MWM) test respectively. A significant increase of both hippocampal klotho expression along with an increase in its downstream effectors AKT and ERK phosphorylation with an inhibition of JAK2/STAT3 pathway were observed. These results were evidenced by an increase in hippocampal Bcl-2 expression and a decrease in hippocampal BAX expression which were subsequently accomplished with reduction in contents of inflammatory, apoptotic and oxidative stress biomarkers as TNF-α, caspase-3 and FOXO1. These findings confirm the neuroprotective role of vildagliptin is via enhancing Klotho protein expression together with activating AKT and ERK pathway and conversely inhibiting JAK/STAT pathway.

Biography:
Rasha Refaat Yossef
Part-Time assistant lecturer at pharmacology and toxicology department, Faculty of pharmacy, October 6 university, Giza, Egypt.
Education: Master’s degree of Pharmaceutical Science, pharmacology and toxicology, faculty of pharmacy, Cairo university, Cairo, Egypt, 2020. Diploma of pharmacology and toxicology, faculty of pharmacy, Cairo university, Cairo, Egypt, 2009. Bachelor of pharmaceutical science, faculty of pharmacy, Cairo university, Cairo, Egypt, 2006.
Publications:
1. Rasha R. Yossef, Ayman E. El-Sahar, Mohamed F. Al-Yamany. Favorable Effects of Vildagliptin on Metabolic and Cognitive Dysfunctions in Drug Induced Alzheimer’s Disease in Rats with Metabolic Syndrome. Poster in the 2nd International Conference of the Faculty of Pharmacy Ain Shams University in November 13TH to November 15TH, 2018, Cairo, Egypt.
2.Rasha R. Yossef, Mohamed F. Al-Yamany, Ayman E. El-Sahar. Neuroprotective Effects of Vildagliptin on Metabolic and Cognitive Dysfunctions in Drug Induced Alzheimer’s Disease in Rats with Metabolic Syndrome: Role of Hippocampal Klotho and AKT Signalling Pathways. Poster in the 2nd World Congress and Expo on Toxicology and Pharmacology, organized by Biocore conferences in October 28TH to October 29TH, 2019, Rome, Italy.
3.Yossef, R.R., El-Yamany, M.F., Saad, M.A., El-Sahar, A.E.: Neuroprotective Effects of Vildagliptin on Metabolic and Cognitive Dysfunctions in Drug Induced Alzheimer’s Disease in Rats with Metabolic Syndrome: Role of Hippocampal Klotho and AKT Signalling Pathways. An article published by The European journal of pharmacology 889 (2020), 173612.
Attended Conferences: Attended the 2nd International Conference of the Faculty of Pharmacy Ain Shams University in November 13TH to November 15TH, 2018, Cairo, Egypt, for the poster presentation.

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