Antiparkinsonian Action of the Prolyl Endopeptidase Inhibitor in Mice

Kalinina, A. P.; Kapitsa, I. G.; Ivanova, Elena; Воронина, Т. А.

doi:10.3103/s0096392519020044

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Other known bioactivities attributed to BPs found in the samples include opioid effect and delayed cognitive decline along with inhibition of prolyl-endopeptidase and cathepsin B. These latter effects, combined, could be useful in delaying the progression of tumors ( Lee and Lee, 2000 ; Perez et al, 2020 ) and fighting the onset and development of Parkinson’s disease ( Kalinina et al, 2019 ). A potential beneficial effect of cheese consumption on cardiovascular health related to the presence of potential BP, or their release after digestion, had already been hypothesized by other authors ( Petyaev and Bashmakov, 2012 ; Hjerpsted and Tholstrup, 2016 ; Sultan et al, 2018 ) and for PR ( Basiricò et al, 2015 ; Martini et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Peptide profile of Parmigiano Reggiano cheese after simulated gastrointestinal digestion: From quality drivers to functional compounds

et al. 2022

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Time of ripening has a strong impact on shaping the valuable and recognizable characteristics of long-ripened types of cheese such as Parmigiano Reggiano (PR) due to the interrelationship between microbiota and proteolysis that occurs during ripening. The derived peptide profile is linked to cheese quality and represents the canvas for enzymes upon digestion, which could be responsible for the release of potentially bioactive peptides (BPs). In this study, we aimed at investigating the presence of BP in 72 PR cheese samples of different ripening times, from curd to 24 months of ripening, produced in six different dairies, and following their fate after simulated gastrointestinal digestion. A small number of peptide sequences sharing 100% similarity with known antimicrobial, antioxidant, and ACE-inhibitor sequences were found in PR cheeses, while a higher number of potential BPs were found after their simulated gastrointestinal digestion, in different amounts according to ripening time. Taking advantage of the complex organization of the sampling plan, we were able to follow the fate of peptides considered quality drivers during cheese ripening to their release as functional compounds upon digestion.

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Section: Resultsmentioning

confidence: 99%

Peptide profile of Parmigiano Reggiano cheese after simulated gastrointestinal digestion: From quality drivers to functional compounds

et al. 2022

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“…We found that administration of POP inhibitors, including BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, and CbzGlnPrdN, significantly improved scopolamine- and MES-induced memory impairments in the CPAR model, with the most potent being CbzMetPrdN. It should be noted that CbzMetPrdN was previously studied in a preclinical model of Parkinsonian syndrome, where it exhibited neuroprotective activity and abolished depressive symptoms caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ( Khlebnikova et al, 2009b ; Krupina et al, 2009 ; Khlebnikova et al, 2012 ; Khlebnikova et al, 2013a ; Khlebnikova et al, 2013b ; Kalinina et al, 2019 ; Krupina et al, 2013b ). Thus, CbzMetPrdN would be an ideal compound to evaluate in other models of CNS disease.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia

et al. 2021

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Prolyl oligopeptidase (POP) is a large cytosolic serine peptidase that is altered in patients with Alzheimer’s disease, Parkinsonian syndrome, muscular dystrophies, and other denervating diseases. Thus, POP may represent a relevant therapeutic target for treatment of neuropsychiatric disorders and neurodegenerative diseases. Here, we report the characterization of five novel cyanopyrrolidine-based compounds (BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, CbzGlnPrdN, and CbzAlaPrdN) and show that they are potent inhibitors of POP and are predicted to penetrate the blood-brain barrier (BBB). Indeed, we show that CbzMetPrdN penetrates the rat BBB and effectively inhibits POP in the brain when administered intraperitoneally. Furthermore, molecular modeling confirmed these compounds likely inhibit POP via interaction with the POP catalytic site. We evaluated protective effects of the cyanopyrrolidine-based POP inhibitors using scopolamine- and maximal electroshock-induced models of amnesia in rats and showed that BocTrpPrdN, BocGlyPrdN, CbzMetPrdN, and CbzGlnPrdN significantly prolonged conditioned passive avoidance reflex (CPAR) retention time when administered intraperitoneally (1 and 2 mg/kg) before evaluation in both models of amnesia, although CbzAlaPrdN was not effective in scopolamine-induced amnesia. Our data support previous reports on the antiamnesic effects of prolinal-based POP inhibitors and indicate an important role of POP in the regulation of learning and memory processes in the CNS.

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“…ПЭП является конститутивным ферментом нейтрофилов периферической крови человека, способным расщеплять коллаген с образованием нейтрофильного хемоаттрактанта пролин-глицилпролина [3], уровень которого повышен при хроническом нейтрофильном воспалении дыхательных путей [4]. ПЭП расщепляет вещество Р (SP(1-11) с С-конца с образованием фрагментов SP (3)(4)(5)(6)(7)(8)(9)(10)(11), SP (5)(6)(7)(8)(9)(10)(11) и SP (8)(9)(10)(11) [5], которые отвечают за ноцицептивный эффект вещества Р [6].…”

Section: Introductionunclassified

“…Производное цианопирролидина бензилоксикарбонил-метионил-цианопирролидин (ZMetPrdN) -является неконкурентным ингибитором ПЭП [7] и проявляет нейропротекторную активность на модели паркинсонического синдрома, вызванного однократным системным введением мышам C57Bl/6 нейротоксина 1-метил-4-фенил-1,2,3,6-тетрагидропиридина в дозе 30 мг/кг, не влияя непосредственно на дофаминергическую систему животных [8].…”

Section: Introductionunclassified

Effect of cyanopyrrolidine derivatives on the activity of prolylendopeptidase, acute exudative inflammation and visceral pain in mice

et al. 2020

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Cyanopyrrolidine derivatives benzyloxycarbonyl-methionyl-cyanopyrrolidine (ZMetPrdN), benzyloxycarbonylphenylalanyl- cyanopyrrolidine (ZPhePrdN), tert-butyl-hydroxycarbonyl-glycyl-cyanopyrrolidine (BocGlyPrdN), tert-butyl-hydroxycarbonyl-methionyl-cyanopyrrolidine (BocMetPrdN) are inhibitors of prolylendopeptidase (PREP; EC 3.4.21.26) with an IC50 of 2 nM to 12 nM. ZMetPrdN, ZPhePrdN and BocMetPrdN additionally inhibited dipeptidyl peptidase IV (DPP-4; EC 3.4.14.5) with an IC50 of 1100 nM to 3200 nM. All the compounds have antinociceptive properties in the acetic acid writhing test in mice. But only cyanopyrrolidine derivatives with aromatic substituents decrease exudative inflammation. The cyanopyrrolidine derivatives also increase PREP activity and compensatorily reduce DPP-4 activity in the serum of mice three hours after the induction of inflammation. Thus, cyanopyrrolidine derivatives exhibit antinociceptive and antiexudative properties in part via their effect on PREP.

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Antiparkinsonian Action of the Prolyl Endopeptidase Inhibitor in Mice

Cited by 7 publications

References 15 publications

Peptide profile of Parmigiano Reggiano cheese after simulated gastrointestinal digestion: From quality drivers to functional compounds

Peptide profile of Parmigiano Reggiano cheese after simulated gastrointestinal digestion: From quality drivers to functional compounds

Therapeutic Effect of Novel Cyanopyrrolidine-Based Prolyl Oligopeptidase Inhibitors in Rat Models of Amnesia

Effect of cyanopyrrolidine derivatives on the activity of prolylendopeptidase, acute exudative inflammation and visceral pain in mice

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