Figure 4.

Highlighting the neuroprotective role of Substance P in Parkinson’s disease. SP upon interaction with NK1 receptor, decreases Ca²⁺ entry, caspase-3 stimulation, ROS formation, and modulates MtMP, which in turn inhibit programmed cell death and cytotoxicity, and thereby protects MES23.5 cells from MPP⁺-prompted neurotoxicity. Septide, an analog of SP, upon interaction with NK1 receptor culminates in the suppression of programmed cell death pathways and stimulation of PKB/Akt signaling pathway, thereby protects nerve cells against 6-OHDA-prompted neurotoxicity. Further, senktide, upon interaction with NK3 receptor, reinstated the temporal order memory in the 6-OHDA-lesioned hemiparkinsonian rat model. In addition, the three NK1 receptor antagonists, namely NAT, L-733060, and LY303870, upon introduction, decrease cellular demise provoked by 6-OHDA subjection, upgrade motor operations, and decrease levodopa-precipitated dyskinesia. Finally, by virtue of these mechanisms, SP markedly contributes to neuroprotective action in PD. Subtraction symbol indicates inhibitory/suppressing action, while addition symbol indicates stimulatory action. SP, Substance P; NAT, N-acetyl-L-tryptophan; LY303870, lanepitant; NK, neurokinin; NK1, neurokinin 1; NK3, neurokinin 3; Ca²⁺, calcium ions; ROS, reactive oxygen species; MtMP, mitochondrial membrane potential; MES23.5, DArgic nerve cell line; MPP⁺, 1-methyl-4-phenylpyridinium ion; PKB/Akt, protein kinase B signaling pathway; 6-OHDA, 6-hydroxy DA; PD, Parkinson’s disease; ↓, decreasing or reducing.