Evaluation of the neuroprotective potential in MPP⁺ -induced neurodegeneration of the new heterocyclic compounds based on pyrazolopyridine scaffold

Parkinson's disease is the second most common neurodegenerative disorder affecting millions of individuals worldwide. In this study we present new potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then we evaluate their effects in MPP⁺ -induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP⁺ - induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 mM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways.