Inhibitors of prolyl oligopeptidase have been reported to be neuroprotective, especially in memory loss caused by lesion or disease. This enzyme has also been implicated in neurodegeneration. Although it was initially thought that prolyl oligopeptidase functioned to directly control of neuropeptide levels, emerging evidence points out in part that this peptidase modulates peptides which in turn regulate inflammatory responses. Here we review the recent literature which indicates a direct involvement of prolyl oligopeptidase in several inflammatory diseases. Neuroinflammation generates neurotoxins with a relevant role in neurodegenerative diseases, and it is within this toxin generation where prolyl oligopeptidase might have a role.

BackgroundOppositional Defiant Disorder (ODD) is characterized by angry and noncompliant behaviour. It is the most common disruptive behaviour disorder (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked to several long-term difficulties, including disorders of conduct, mood, anxiety, impulse-control, and substance abuse. ODD in children is related to parental depression, family dysfunction, and impairments in parental work performance. Children displaying early DBDs exhibit more symptoms of greater severity, more frequent offences, and commit more serious crimes later in life. The goal of the Strongest Families™ Finland Canada (SFFC) Smart Website intervention research program is to develop and evaluate an affordable, accessible, effective secondary prevention parent training program for disruptive behaviour in preschoolers to prevent the negative sequelae of ODD. Strongest Families is an 11-session program with two booster sessions that focuses on teaching skills to: strengthen parent–child relationships; reinforce positive behaviour; reduce conflict; manage daily transitions; plan for potentially problematic situations; promote emotional regulation and pro-social behaviour and decrease antisocial behaviour.Methods/designThis protocol paper describes an ongoing population-based randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child clinics in Turku, Finland and environs to examine the effectiveness of the Strongest Families Smart Website intervention compared to an Education Control condition. Randomization consists of a 1:1 ratio for intervention versus the education group, stratified by the child’s sex. The participants randomized to the intervention group receive access to the Strongest Families Smart Website and weekly telephone coaching sessions. The participants randomized to the Education Control condition receive access to a static website with parenting tips. Children are followed using parental and daycare teacher measures at 6 and 12 months after randomization.DiscussionThe Strongest Families Smart Website intervention is hypothesized to improve parenting skills, reduce child disruptive behaviour, reduce parental distress and improve family functioning. These results will likely inform subsequent investigations, public policy, and early treatment of childhood disruptive behaviour problems.Trial registrationClinicalTrials.gov # NCT01750996