Targeting CB 1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease

摘要: Cannabinoid CB1 receptors (CB1R) and the GPR55 receptor are expressed in striatum potential targets therapy of Parkinson's disease (PD), one most prevalent neurodegenerative diseases developed countries. The aim this paper was to address ligands acting on those prevent action a neurotoxic agent, MPP+, that specifically affects neurons substantia nigra due uptake via dopamine DAT transporter. SH-SY5Y cell line model used as it expresses and, therefore, is able MPP+ inhibits complex I respiratory mitochondrial chain leads death. Cells were transfected with cDNAs coding for either or both receptors. Receptors cotransfected cells formed heteromers indicated by situ proximity ligation assays. Cell viability assayed oxygen rate consumption bromide-based MTT method. Assays neuroprotection using two concentrations showed expressing more resistant toxic effect. After correction effects proliferation, CB1R antagonist, SR141716, afforded an almost full CB1R-expressing even when selective agonist, ACEA, present. In contrast, SR141716 not effective CB1/GPR55 heteromeric complexes. addition, agonist GPR55, CID1792197, did enhance GPR55-expressing cells. These results show death but question real usefulness CB1R, their afford PD-related neuroprotection.