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Glutamate-induced neuronal cell death plays a key role in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Some recent studies reported the potential immunomodulatory and neuroprotective properties of inhibitors of serine-threonine kinase, mTOR (mammalian target of rapamycin). However, no study was conducted about the neuroprotective potential of everolimus (EVR), a selective and potent mTOR inhibitor. Therefore, this study was planned to investigate whether EVR has protective effects against glutamate-induced toxicity in PC12 cells, which are used as model for neurons injury, and to elucidate the underlying mechanism. PC12 cells were concurrently treated with glutamate (8 mM) and EVR (0-40 nM) for 24 h. Then, the cells viability, apoptosis rate, and apoptosis-related proteins (caspase-3, bax and bcl-2) were measured using MTT, annexin V/PI and immunoblotting assays. Analyzing the protective effect of different concentrations of EVR (0-40 nM) against glutamate-induced cytotoxicity revealed a significant increase in cell viability in co-treatment regimen ( p  &lt; 0.01). Also, EVR (40 nM) significantly ( p  &lt; 0.01) inhibited glutamate-induced apoptosis through depressing the elevation of bax/bcl-2 ratio and expression of cleaved caspase-3, concentration depend. The results demonstrated, for the first time, that EVR could protect against glutamate-mediated PC12 cell death  via  inhibiting apoptosis.

Everolimus attenuates glutamate-induced PC12 cells death