Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis

Peer reviewe

The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients

Abstract Background Liver failure in experimental animals or in human cirrhosis elicits neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory events in neurodegenerative diseases: PREP protein levels are increased in brain glial cells upon neuroinflammatory insults, but the circulating PREP activity levels are decreased in multiple sclerosis patients in a process probably mediated by bioactive peptides. In this work, we studied the variation of PREP levels upon liver failure and correlated it with several inflammatory markers to conclude on the relation of PREP with systemic and/or neuroinflammation. Methods PREP enzymatic activity and protein levels measured with immunological techniques were determined in the brain and plasma of rats with portacaval shunt (PCS) and after treatment with ibuprofen. Those results were compared with the levels of PREP measured in plasma from cirrhotic patients with or without minimal hepatic encephalopathy (MHE). Levels of several pro-inflammatory cytokines and those of NO/cGMP homeostasis metabolites were measured in PCS rats and cirrhotic patients to conclude on the role of PREP in inflammation. Results In PCA rats, we found that PREP levels are significantly increased in the hippocampus, striatum and cerebellum, that in the cerebellum the PREP increase was significantly found in the extracellular space and that the levels were restored to those measured in control rats after administration of an anti-inflammatory agent, ibuprofen. In cirrhotic patients, circulatory PREP activity was found to correlate to systemic and neuroinflammatory markers and had a negative correlation with the severity of the disease, although no clear relation to MHE. Conclusions These results support the idea that PREP levels could be used as indicators of cirrhosis severity in humans, and using other markers, it might contribute to assessing the level of neuroinflammation in those patients. This work reports, for the first time, that PREP is secreted to the extracellular space in the cerebellum most probably due to glial activation and supports the role of the peptidase in the inflammatory response

A cross-cultural survey to identify Seniors’ preferences towards the Empathic Virtual Coach

The present investigation is part of the EMPATHIC project aiming at develop an Empathic Virtual Coach (VC) able to promote seniors' healthy lifestyle and independent aging. To this end, it is fundamental to investigate users' preferences towards the implemented automatic system refined on the basis of users' preferences derived from previous field trials with Wizard of Oz (WoZ) experimental sessions. Data collection has been carried out involving three different countries (France, Norway and Spain) and a total of 71 volunteers was enrolled in the planned field trials. Five Virtual Agents (VAs) named Natalie, Alice, Lena, Christian and Adam were purposely designed and users' preferences were assessed using the shortened version of the Virtual Agent Acceptance Questionnaire (VAAQ). This specific tool, developed by members of the EMPATHIC project, includes 7 different sections, and the present work aims to disseminate results of four of the seven sections administered to participants, devoted at assessing respectively: users' willingness to interact (section II); pragmatic, hedonic (Identity and Feeling) and attractiveness qualities (section III); the type of task participants entrusted to the proposed agents among healthcare, housework, protection/security, and front office jobs (section V) and agents voice' quality (section VI). Results reveal seniors' appreciation of agents' pleasantness, originality, voice' quality and ability to engage users in a long lasting interaction with them

Issues About the Physiological Functions of Prolyl Oligopeptidase Based on Its Discordant Spatial Association With Substrates and Inconsistencies Among mRNA, Protein Levels, and Enzymatic Activity

Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline-containing peptides shorter than 30 amino acids. POP may be associated with cognitive functions, possibly via the cleavage of neuropeptides. Recent studies have also suggested novel non-hydrolytic and non-catalytic functions for POP. Moreover, POP has also been proposed as a regulator of inositol 1,4,5-triphosphate signaling and several other functions such as cell proliferation and differentiation, as well as signal transduction in the central nervous system, and it is suspected to be involved in pathological conditions such as Parkinson's and Alzheimer's diseases and cancer. POP inhibitors have been developed to restore the depleted neuropeptide levels encountered in aging or in neurodegenerative disorders. These compounds have shown some antiamnesic effects in animal models. However, the mechanisms of these hypothesized actions are still far from clear. Moreover, the physiological role of POP has remained unknown, and a lack of basic studies, including its distribution, is obvious. The aim of this review is to gather information about POP and to propose some novel roles for this enzyme based on its distribution and its discordant spatial association with its best known substrates. (J Histochem Cytochem 57:831–848, 2009

The EMPATHIC Project: Building an Expressive, Advanced Virtual Coach to Improve Independent Healthy-Life-Years of the Elderly

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