Our studies also unravel the downstream signaling pathways through which TRPC1 promotes neuronal survival induced by specific HDAC inhibitors a neurotoxin that mimics PD. We discovered that MPP decreases AKT1 activation by decreasing cellular levels of phosphorylated AKT1, which can be in line with previous reports showing that PD causing neurotoxins including MPP and 6 OHDA decrease phospho AKT. Apparently, TRPC1 overexpression prevented MPTP/MPP mediated lack of AKT1 purpose by increasing its phosphorylation. AKT1 represents a major part in neuronal survival by phosphorylating its substrates, including forkhead meats, GSK3, NF?B, and BAD, and AKT1 over-expression has been shown to drive back MPP.. TRPC1 overexpression triggers the phosphorylation of AKT at both Ser473 and Thr308, which are essential for complete activation of AKT1. Although addition of external Ca2 restored, AKT1 phosphorylation, since treatment of external Ca2 avoided, also, Ca2 influx via TRPC1 was essential for the activation of AKT1. Likewise, the TRPC1pm was unable to trigger AKT1 phosphorylation in MPP treated cells. These Meristem studies were further confirmed by the usage of pharmacological TRPC channel activators and its inhibitor. Initial of TRPC1 by CCh and Tg resulted in increased phospho AKT1, whereas pre-treatment with SKF 96365 considerably stopped TRPC1 mediated AKT1 phosphorylation. Moreover, TRPC1 exerted neuroprotection via AKT activation, because silencing AKT1 abolished TRPC1 mediated neuroprotection in SH SY5Y cells. We can’t rule out the possibility that the launch of BDNF under these conditions is also not altered, while no escalation in BDNF expression was seen in TRPC1 overexpressing cells treated with MPP. In line with Fingolimod distributor the in vitro studies, we discovered that overexpression of TRPC1 inside the mouse SNpc also led to rescue of MPTP mediated loss of DA neurons. We previously reported that MPTP treatment decreases the expression of TRPC1. In line with this, today’s study also showed that MPTP therapy significantly decreased TRPC1 expression and increased activation of UPR markers in the SNpc. Growing evidence also shows the significance of the mTOR pathway in autophagy and apoptosis that often leads to neuronal death, however in each one of these circumstances it was the inhibition of the AKT phosphorylation, rather than mTOR service, that ultimately resulted in neuronal loss. Our present that MPTP represses the phosphorylation of AKT, mTOR, p70 S6 kinase, and 4EBP1 and that loss of AKT leads to neuronal loss. Notably, mTOR kinases are downstream of the AKT pathway and have been shown to have a double part, nevertheless, it’s the activation of the AKT pathway that may phosphorylate mTOR differently that may have a good influence rather than leading to neuronal loss, as noticed in some of these studies. ER pressure induced by tunicamycin has shown to downregulate the game of AKT and mTOR and induced apoptosis in rat hippocampal neurons.