Neurosteroid metabolites of testosterone and progesterone differentially inhibit ERK phosphorylation induced by amyloid β in SH-SY5Y cells and primary cortical neurons

RETRACTED: Allopregnanolone Modulates GABAAR-Dependent CaMKIIδ3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage

“…Moreover, the action of APα has been shown to activate GABAAR-driven VGLCC and subsequent increases of intracellular Ca 2+ concentration (Keller et al, 2004;Wang et al, , 2010Wang and Brinton, 2008;Jagasia et al, 2009;Chen S. et al, 2011;Frye et al, 2014), which was in accordance with our current study. In addition, we also cannot rule out the possibility that APα interacts with the pregnane-X-receptor or membrane progesterone G-protein coupled receptor to regulate its neuroprotective process (Charalampopoulos et al, 2008;Mendell et al, 2018;Taleb et al, 2018). Mendell et al (2018) also suggested a model for neurosteroid actions included both GABAAR-dependent and GABAAR-independent mechanisms.…”

“…In addition, we also cannot rule out the possibility that APα interacts with the pregnane-X-receptor or membrane progesterone G-protein coupled receptor to regulate its neuroprotective process (Charalampopoulos et al, 2008;Mendell et al, 2018;Taleb et al, 2018). Mendell et al (2018) also suggested a model for neurosteroid actions included both GABAAR-dependent and GABAAR-independent mechanisms. These existing controversies reflect not only the different concentrations of neurosteroids but also the specific cell culture conditions.…”

“…These existing controversies reflect not only the different concentrations of neurosteroids but also the specific cell culture conditions. In addition, the type of GABAAR antagonist and the composition of the GABAAR subunit contributed to these conflicting results Afroz et al, 2017;Mendell et al, 2018).…”

Neurosteroid Metabolites of Gonadal Steroid Hormones in Neuroprotection: Implications for Sex Differences in Neurodegenerative Disease

“…Interestingly, while the 3α-hydroxy conformation appears to be required to stimulate proliferation, 3β isomers of allopregnanolone and synthetic analogs (3-O-allyl-allopregnanolone) have been shown to protect hippocampal neurons, neural stem cell cultures, and SH-SY5Y human female neuroblastoma cells from neurotoxicity induced by amyloid β peptide 1-42 (Aβ42) or hydrogen peroxide (H 2 O 2 ; Karout et al, 2016 ; Lejri et al, 2017 ). The mechanisms of allopregnanolone and its analogs on neuroprotection in vitro appear to have both GABA A receptor-dependent and -independent components, as these neurosteroids are able to exert protective effects against Aβ42 or H 2 O 2 -induced toxicity in the absence of functional GABA A receptors (Lejri et al, 2017 ; Mendell et al, 2018 ); although allopregnanolone appears to be more effective at lower concentrations in the presence of functional GABA A receptors (Grimm et al, 2014 ; Karout et al, 2016 ; Mendell et al, 2018 ). Further studies are required in order to better characterize the GABA A receptor-independent mechanisms by which allopregnanolone may provide neuroprotection.…”

“…Physiological concentrations of 3α-diol are able to protect SH-SY5Y neuroblastoma cells and primary cortical neurons isolated individually from male and female mice against neurotoxicity induced by H 2 O 2 or Aβ42 (Mendell et al, 2016 , 2018 ; Figure 2 ). This protection appeared to occur through 3α-diol-mediated inhibition of prolonged ERK phosphorylation induced by the neurotoxins, and was associated with a reduction in caspase-3 activation and cell death (Mendell et al, 2016 ; Figure 2 ).…”