Antiparkinsonian Action of the Prolyl Endopeptidase Inhibitor in Mice
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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.
Keywords:prolyl endopeptidase prolyl endopeptidase inhibitors Parkinson-like syndrome mice Parkinson’s disease neurodegeneration.
The study was conducted within the state task, project no. 0521–2019–0007.
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interests. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. Animals were kept according to Sanitary Epidemiological Requirements to the Organization, Equipment, and Maintenance of Biological Experimental Clinics (Vivariums), sanitary regulation no. 22.214.171.12418–14, August 29, 2014, no 51. The work was organized and performed according to international and Russian legal documents: Order of the Ministry of Health of the Russian Federation no. 199n, January 1, 2016 “On Approval of the Rules of Good Laboratory Practice” and the Directive of the European Parliament and of the Council 2010/63/EU, September 22, 2010 “On Protection of Animals Used for Scientific Purposes.” Experiments were approved by the Biomedical Ethics Committee of Zakusov Research Institute of Pharmacology.
The study was conducted in accordance with the Preclinical Study Manual for Drugs (Methodological Recommendations on Preclinical Trial of Drugs with Antiparkinsonian Activity, 2012) .
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