TRPC1 mediated neuroprotection against ER stress induced neurodegeneration correlated with its capability to maintain ER Ca2 homeostasis, since the TRPC1 pore mutant did not save SH SY5Y cells from MPP induced ER stress and cell death. We observed that inhibition of SOC supplier Avagacestat mediated Ca2 entry by MPP leads to a decline in ER Ca2, which in turn induces ER stress. Our data substantiate recent reports indicating that MPP induces ER stress through a procedure relating to the depletion of ER Ca2.. Notably, stopping TRPC channel action or TRPC1 silencing, but not TRPC3 silencing, activates the UPR pathway. In line with these, the UPR indicators were notably improved within the midbrain region of Trpc1?/? Rats, and there was a substantial decline in SOC mediated Ca2 access and TH positive neurons. These are important, since they highlight for the first time to our knowledge that both TRPC1 silencing or inhibition of TRPC channel activity activates ER anxiety by altering SOC mediated Ca2 entry, which contributes to a decline in ER Ca2.. We further declare that the MPP induced ER Ca2 depletion is directly influenced by TRPC1 mediated changes in Ca2 entry. Moreover, silencing of STIM1 also triggered the UPR in SH SY5Y cells. STIM1 can be an ER Ca2 binding protein that senses ER Ca2 amounts, and upon shop depletion, STIM1 aggregates and interacts with Ribonucleotide TRPC1 and Orai1 channels, therefore activating SOCmediated Ca2 entry. Curiously, STIM1 has also been shown to inactivate voltage gated channels, and Ca2 entry via the voltage gated channels has been shown to be deleterious for DA neurons. Hence, it is possible that activation of TRPC1 via its interaction with STIM1 can prevent voltage-gated channels and thus protect DA neurons. The documentation of the importance of TRPC1 in neuroprotection against store depletion?induced ER stress by MPTP/ MPP is, to our c-Met inhibitor understanding, a novel aspect of this study, as it lends credence to previous studies pointing to some function of TRPC channels within the SNpc. Ca2 trend through TRPC stations seems to be described as a essential part of the signaling cascade that mediates growth cone guidance and survival of neurons in response to several growth factors. Specifically, recent studies have reveal the effect of TRPC channels in the SNpc against Tat neurotoxicity. Our previous studies also show the action of TRPC1 against in vitro cell culture types of PD, but, the precise mechanisms where TRPC1 regulates neuronal survival remained poorly understood. In this study, we showed that TRPC1 overexpression confers protection against ER anxiety in both in vivo and in vitro models of PD. TRPC1 over-expression, although not a TRPC1 pore mutant that’s reduced permeability to Ca2, prevented MPP mediated cell death by inhibiting the elevation of CHOP and JNK.