İnsan Nöroblastoma Hücre Kültüründe Amiloid Beta ile Oluşturulan Alzheimer Hastalığı Modelinde Atorvastatinin Sestrin-2, Sirtuin-1, TPP1 ve LC3B Ekspresyonuna Etkisi.

Abstract

Çelik, H. The Effect of Atorvastatin on Sestrin-2, Sirtuin-1, TPP1 and LC3B in Amyloid Beta Induced Alzheimer’s Disease Model in Human Neuroblastoma Cell Culture. Hacettepe University Graduate School of Health Sciences, M.Sc. Thesis in Pharmacology, Ankara, 2019. Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) peptides and the formation of neurofibrillary tangles in the brain, accompanied by neuronal loss and inflammation, decreased cognitive functions and dementia. Disorders in lipid metabolism are thought to be associated with the development of AD. The fact that cholesterol affects the formation of Aβ from amyloid precursor protein (APP) reveals the need for investigating the pathogenesis of AH in terms of Aβ-cholesterol pathways. Recent studies have shown that there is a close relationship between the pathology of AH and autophagy pathways. Autophagy is a vital in the cleavage and removal of protein aggregates, such as Aβ, which is the reason of AD pathology, by lysosomal destruction. The aim of this study was to investigate the role of cholesterol-related pathways in sestrin-2 (SESN2), sirtuin-1 (SIRT1), a lysosomal enszyme tripeptidyl peptidase 1 (TPP1) ve microtubule associated protein light chain-3 (LC3B) proteins, which are thought to be responsible for antioxidant and autophagy-inducing mechanisms. Aβ (10 μM) applied to human neuroblastoma (SH-SY5Y) cell line and increased SESN2 expression, decreased SIRT1 expression. Co-administration of atorvastatin (1μM) has been shown to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme and lipid peroxidation indicator malondialdehyde (MDA) in these cells. The autophagy marker LC3B increased with co-administration of Aβ (10 μM) and atorvastatin (1μM). No change has been shown in the levels of the lysosomal enzyme TPP1. In this thesis, we can conclude that atorvastatin has a pharmacological effect during Aβ damage by regulating the expression of SESN2, SIRT1 and LC3B proteins as well as HMG-CoA reductase enzyme inhibitor and antioxidant effect.