Effect of atorvastatin on Aβ1–42-induced alteration of SESN2, SIRT1, LC3II and TPP1 protein expressions in neuronal cell cultures

Abstract

Objectives Sestrins (SESNs) and sirtuins (SIRTs) are antioxidant and antiapoptotic genes and crucial mediators for lysosomal autophagy regulation that play a pivotal role in the Alzheimer's disease (AD). Recently, statins have been linked to the reduced prevalence of AD in statin-prescribed populations yet molecular basis for the neuroprotective action of statins is still under debate. Methods This study was undertaken whether Ab-induced changes of SESN2 and SIRT1 protein expression, autophagy marker LC3II and lysosomal enzyme TPP1 affected by atorvastatin (Western blot) and its possible role in Ab neurotoxicity (ELISA). Key findings/results We showed that SESN2 and LC3II expressions were elevated, whereas SIRT1 and TPP1 expressions were decreased in the Ab 1-42 -exposed human neuroblastoma cells (SH-SY5Y). Co-administration of atorvastatin with Ab 1-42 compensates SESN2 increase and recovers SIRT1 decline by reducing oxidative stress, decreasing SESN2 expression and increasing SIRT1 expression by its neuroprotective action. Atorvastatin induced LC3II but not TPP1 level in the Ab 1-42 -exposed cells suggested that atorvastatin is effective in the formation of autophagosome but not on the expression of the specific lysosomal enzyme TPP1. Discussion and conclusion Together, these results indicate that atorvastatin induced SESN2, SIRT1 and LC3II levels play a protective role against Ab 1-42 neurotoxicity.

Statins and Alzheimer — current stand and further development directions

“…He based his conclusions on the results of studies that showed that COX-1 inhibitors with anti-inflammatory effects slow down cognitive decline while reducing Ab platelets [22]. Sun and colleagues also came to the same conclusions, who showed that the amyloid-beta solution induces an increase in TNF-alpha and IL-6 levels [16]. Moreover, the amyloid b peptide has been shown to increase microglia activation by increasing the production of inflammatory cytokines interleukin-1b (IL-1b), interleukin-6 (IL-6) and tumor necrosis factor a (TNF-a) [30].…”

“…However, due to their pleiotropic effect, we should not limit their use. Experimental studies have shown that statins reduce Ab production, inhibit inflammatory reactions, protect neurons from neurotoxicity induced by pathological protein, and oxidative stress [8,16]. We divide statins according to their properties.…”

“…Research in 2019 [54] aimed to show the relationship between the levels of Sestryn, Sirtuin and statins. Researchers chose these proteins because of their potential neuroprotective mechanisms that could prevent amyloid beta-induced neurodegeneration.…”

“…Atorvastatin has been found to enhance the expression of the SIRT1 protein. youth protein, which protects neurons [54]. Hence, this work [54] undertook to measure the level of this protein.…”

Celecoxib Exerts Neuroprotective Effects in β-Amyloid-Treated SH-SY5Y Cells Through the Regulation of Heme Oxygenase-1: Novel Insights for an Old Drug

“…On these premises, the first aim of this work is to fully characterize, by using a pharmacological approach, the differential regulation of the HO/BVR system by both sAβ and fAβ in the human neuroblastoma SH-SY5Y cells, a reliable experimental system widely used to study neurodegeneration and AD ( Marrazzo et al, 2019 ; Wang et al, 2019 ; Celik et al, 2020 ). Furthermore, since in vivo data have shown that the COX-2 inhibitor celecoxib (CXB) reduces neuroinflammation and prevents cognitive impairment and behavioral abnormalities in sAβ-treated rats, the second aim of this work is to investigate whether or not CXB modulates the HO/BVR system in SH-SY5Y cells, thus widening the spectrum of its therapeutic activity.…”