PREP is an interesting candidate gene to investigate in genetic studies of BD, but our findings do not support the hypothesis that genetic variation in this gene plays a major role in the etiology of BD or Li response.
It describes the identification of prolyl oligopeptidase in D. discoideum as a modulator of inositol phosphate signalling, and the subsequent identification of a common mechanism of action of three anti-manic drugs in mammalian neurons.
This unexpected result suggests a model that could explain the dual action of VPA in stabilizing mood: we propose that euthymic mood is dependent on stable PIns signaling and that VPA may limit mood swings to mania by decreasing PIns signaling, and that it may limit mood swings to depression by inhibiting PO and thus increasing PIns signaling.
New prolyl endopeptidase inhibitors: in vitro and in vivo activities of azabicyclo[2.2.2]octane, azabicyclo[2.2.1]heptane, and perhydroindole derivatives.
(Neurobiol Dis 2014;68:1-15) describe a prolyl oligopeptidase inhibitor that reduces α-synuclein species related to Parkinson's disease and other α-synucleinopathies, and this inhibitor caused a concomitant increase in autophagic activation markers.
These results demonstrate that PEP-1-HSP27 provides a potential strategy for therapeutic delivery against various diseases and is a potential tool for the treatment of PD.
The aggregation of α-synuclein is connected to the pathology of Parkinson's disease and prolyl oligopeptidase (PREP) accelerates the aggregation of α-synuclein in vitro.
We have previously found that PREP negatively regulates beclin1-mediated macroautophagy (autophagy), and that PREP inhibition by a small-molecule inhibitor induces clearance of protein aggregates in Parkinson's disease models.
Prolyl oligopeptidase (POP) is a potential therapeutic target for treatment of several neurological disorders and α-synucleinopathies including Parkinson's disease.
These results demonstrate the potential for PEP-1-PEA-15 to provide a new strategy for protein therapy treatment of a variety of neurodegenerative diseases including PD.
Over the past decade, many drug discovery endeavors have been invested in targeting the serine proteases prolyl oligopeptidase (POP) for the treatment of Alzheimer's and Parkinson's disease and, more recently, epithelial cancers.
Prolyl oligopeptidase (PREP) inhibition by small-molecule inhibitors can reduce alpha-synuclein (aSyn) aggregation, a key player in Parkinson's disease pathology.
Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a <i>Caenorhabditis elegans</i> model of Alzheimer's disease (AD) was evaluated.
Thus, PREP inhibitors may offer a novel therapeutic approach for the treatment of neurodegenerative disorders with an inflammatory component including Parkinson's and Alzheimer's diseases.
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.
Here we studied the expression, enzymatic activity and subcellular localization of PEP in adult and aged mouse brain as well as in brains of age-matched APP transgenic Tg2576 mice and in brains of Alzheimer's disease patients.
Among them, inhibition of acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase can be beneficial targets in the treatment of Alzheimer's disease.