Neural stem cells neuroprotection by simvastatin via autophagy induction and apoptosis inhibition

Abstract

OBJECTIVE: This study was conducted to investigate the effects of Simvastatin (SIM), a member of statin family, on the cellular antioxidant system, autophagy and apoptosis in NSCs exposed to hydrogen peroxide. BACKGROUND: Reduction in cellular oxidative stress increases the survival of neural stem cells (NSCs) after transplantation into the damaged area of the affected central nervous system. MATERIAL AND METHODS: NSCs derived from bone marrow stromal cells (BMSCs) were exposed to H 2 O 2 (100 μM) for 48 hours after pretreatment with SIM (2 μM). Next, the expressions of the master antioxidant transcription factor, Nrf2/nuclear factor erythroid 2 (NFE2)-related factor 2, autophagy-related proteins (microtubule-associated proteins 1A/1B light chain 3B known as LC3I and LC3II and also p62/ Sequestosome), and apoptosis (Bcl-2/ B-cell lymphoma 2 and Bax/BCL2 associated X protein) were analyzed. RESULTS: SIM caused Nrf2 over-activation (more localizations in the cellular nucleus), reduction in reactive oxygen species (ROS), induction of autophagy (decrease in p62 expression and increase in LC3II/LC3I ratio) and inhibition of apoptosis (decrease in Bax protein and increase in Bcl-2) in NSCs exposed to H 2 O 2-induced oxidative stress, thereby prolonging the cell viability within 48 hours at low concentration (2 μM). CONCLUSION: SIM protects NSCs against H 2 O 2-induced apoptosis in a pleiotropic signaling manner (Fig. 7, Ref. 35).

Early metabolic impairment as a contributor to neurodegenerative disease: Mechanisms and potential pharmacological intervention

“…On the other hand, in vitro experiments showed that statins protected neural stem cells against hydrogen peroxide (H 2 O 2 )‐induced apoptosis by induction of autophagy and reduction of oxidative stress (80). Indeed, statin treatment was shown to improve autophagy and suppress neuronal apoptosis in rat models of brain ischemia (81).…”

Uncovering ferroptosis in Parkinson’s disease via bioinformatics and machine learning, and reversed deducing potential therapeutic natural products

“…The mechanism of QCT is to protect neurons by inhibiting microglial activation (Han et al, 2021). E2 has protective effects against many neurodegenerative diseases and mediates its effects through dopamine receptors (Brann et al, 2007;Varmazyar et al, 2019). A study has shown that E2 can activate autophagy by regulating the expression of UKL1, thereby preventing the α-abnormal accumulation of synuclein and exerting a neuronal protective effect (Varmazyar et al, 2019).…”

“…E2 has protective effects against many neurodegenerative diseases and mediates its effects through dopamine receptors (Brann et al, 2007;Varmazyar et al, 2019). A study has shown that E2 can activate autophagy by regulating the expression of UKL1, thereby preventing the α-abnormal accumulation of synuclein and exerting a neuronal protective effect (Varmazyar et al, 2019). This suggests that QCT and E2 may serve as potent ingredients to explore the regulatory impact on the pathogenesis of ferroptosis in PD.…”