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.
Figure 6. A) Schematic mechanism of TKD@RMPB formation and its US stimulus-responsive antitumor behavior. Reproduced with permission. [76] Copyright 2020, Wiley-VCH. B) Schematic illustration for the preparation and the anticancer mechanism of HPT-DOX. Reproduced with permission. [73] Copyright 2020, Wiley-VCH.
Background/Aims: Decreasing levels of aromatase and seladin-1 could be one of the molecular mechanisms of Alzheimer’s disease (AD). Aromatase is an enzyme that catalyzes estrogen biosynthesis from androgen precursors, and seladin-1 is an enzyme that converts desmosterol to cholesterol, which is the precursor of all hormones. Verifying the potential relationship between these proteins and accordingly determining new therapeutic targets constitute the aims of this study. Methods: Changes in protein levels were compared in vitro in aromatase and seladin-1 inhibitor-administered human neuroblastoma (SH-SY5Y) cells in vivo in intracerebroventricular (icv) aromatase or seladin-1 inhibitor-administered rats, as well as in transgenic AD mice in which the genes encoding these proteins were knocked out. Results and Conclusions: In the cell cultures, we observed that seladin-1 protein levels increased after aromatase enzyme inhibition. The hippocampal aromatase protein levels decreased following chronic seladin-1 inhibition in icv inhibitor-administered rats; however, the aromatase levels in the dentate gyrus of seladin-1 knockout (SelKO) AD male mice increased. These findings indicate a partial relationship between these proteins and their roles in AD pathology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.