Our results also solve the downstream signaling pathways whereby TRPC1 promotes neuronal survival induced by Erlotinib molecular weight a neuro-toxin that mimics PD. We observed that MPP reduces AKT1 activation by reducing cellular levels of phosphorylated AKT1, which is in line with previous reports showing that PD inducing neurotoxins including MPP and 6 OHDA decrease phospho AKT. Apparently, TRPC1 over-expression prevented MPTP/MPP mediated lack of AKT1 purpose by increasing its phosphorylation. AKT1 plays an important role in neuronal survival by phosphorylating its substrates, including GSK3, BAD, NF?B, and forkhead meats, and AKT1 overexpression has been shown to force away MPP.. TRPC1 overexpression initiates the phosphorylation of AKT at both Ser473 and Thr308, that are essential for complete activation of AKT1. Since treatment of external Ca2 avoided, whereas addition of external Ca2 restored, AKT1 phosphorylation, also, Ca2 trend via TRPC1 was necessary for the activation of AKT1. Likewise, the TRPC1pm was unable to trigger AKT1 phosphorylation in MPP treated cells. These Protein biosynthesis results were further confirmed by using its chemical and pharmacological TRPC channel activators. Activation of TRPC1 by Tg and CCh resulted in increased phospho AKT1, while pretreatment with SKF 96365 dramatically prevented TRPC1 mediated phosphorylation. More to the point, TRPC1 exerted neuroprotection via AKT activation, since silencing AKT1 abolished TRPC1 mediated neuroprotection in SH SY5Y cells. We can’t rule out the chance that the release of BDNF under these conditions can also be not altered, while no escalation in BDNF expression was noticed in TRPC1 overexpressing cells treated with MPP. In line with Cabozantinib XL184 the in vitro studies, we discovered that overexpression of TRPC1 inside the mouse SNpc also triggered relief of MPTP mediated loss of DA neurons. We previously noted that MPTP therapy reduces the expression of TRPC1. In line with this, the present study also showed that MPTP therapy significantly reduced TRPC1 expression and increased activation of UPR markers within the SNpc. Increasing evidence also indicates the importance of the mTOR pathway in autophagy and apoptosis that may lead to neuronal death, however in each one of these cases it was the inhibition of the AKT phosphorylation, instead of mTOR activation, that in the course of time resulted in neuronal damage. Our display that MPTP represses the phosphorylation of mTOR, AKT, p70 S6 kinase, and 4EBP1 and that loss of AKT contributes to neuronal loss. Significantly, mTOR kinases are downstream of the AKT pathway and have been proven to have a double position, nevertheless, it is the service of the AKT pathway that may phosphorylate mTOR differently that may have a good result rather than leading to neuronal loss, as noticed in many of these studies. Im anxiety induced by tunicamycin has shown to downregulate the activity of AKT and mTOR and induced apoptosis in rat hippocampal neurons.