Antiparkinsonian Action of the Prolyl Endopeptidase Inhibitor in Mice

Abstract

Prolyl endopeptidase is involved in neurodegeneration, proliferation, neuroinflammation, and neuron differentiation. It has been observed that severity of the neurodegenerative process correlates with an increasing level of prolyl endopeptidase in the brain. According to recent research, prolyl endopeptidase might interact with prion-like proteins, which are believed to play the key role in the development of neurodegenerative diseases. Consequently, prolyl endopeptidase inhibitors might be a promising group of chemicals to study in neurodegenerative diseases, particularly Parkinson’s disease. The aim of this research was to determine the effects of benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine, a new inhibitor of prolyl endopeptidase, using haloperidol catalepsy test in SHK outbred mice and Parkinson-like syndrome induced by a single systemic injection of neurotoxic 1-methyl-4-phenyl-tetrahydropiridine at a dose of 30 mg/kg in C57Bl/6 inbred mice. As a result, the compound reduces the severity of the main extrapyramidal symptoms: rigidity and motor deficits. However, anticataleptic activity was not found. According to our results, the prolyl endopeptidase inhibitor does not affect the dopaminergic neurons directly but provides possible neuroprotection to the neurons.