New tricks of prolyl oligopeptidase inhibitors - A common drug therapy for several neurodegenerative diseases

Show simple item record Svarcbahs, Reinis Julku, Ulrika Kilpelainen, Tommi Kyyrö, Mirva Jäntti, Maria Myohänen, Timo T. 2020-02-29T23:39:26Z 2021-12-17T22:45:11Z 2019-03
dc.identifier.citation Svarcbahs , R , Julku , U , Kilpelainen , T , Kyyrö , M , Jäntti , M & Myohänen , T T 2019 , ' New tricks of prolyl oligopeptidase inhibitors - A common drug therapy for several neurodegenerative diseases ' , Biochemical Pharmacology , vol. 161 , pp. 113-120 .
dc.identifier.other PURE: 123021059
dc.identifier.other PURE UUID: 3325613d-2597-49ee-8ee2-784fad8eda27
dc.identifier.other WOS: 000459236900010
dc.identifier.other Scopus: 85060103819
dc.identifier.other ORCID: /0000-0002-9277-6687/work/55062879
dc.identifier.other ORCID: /0000-0002-1312-9837/work/55063093
dc.description.abstract Changes in prolyl oligopeptidase (PREP) expression levels, protein distribution, and activity correlate with aging and are reported in many neurodegenerative conditions. Together with decreased neuropeptide levels observed in aging and neurodegeneration, and PREP's ability to cleave only small peptides, PREP was identified as a druggable target. Known PREP non-enzymatic functions were disregarded or attributed to PREP enzymatic activity, and several potent small molecule PREP inhibitors were developed during early stages of PREP research. These showed a lot of potential but with variable results in experimental memory models, however, the initial excitement was short-lived and all of the clinical trials were discontinued in either Phase I or II clinical trials for unknown reasons. Recently, PREP's ability to form protein-protein interactions, alter cell proliferation and autophagy has gained more attention than earlier recognized catalytical activity. Of new findings, particularly the aggregation of alpha-synuclein (aSyn) that is seen in the presence of PREP is especially interesting because PREP inhibitors are capable of altering aSyn-PREP interaction in a manner that reduces the aSyn dimerization process. Therefore, it is possible that PREP inhibitors that are altering interactions could have different characteristics than those aimed for strong inhibition of catalytic activity. Moreover, PREP co-localization with aSyn, tau, and amyloid-beta hints to PREP's possible role not only in the synucleinopathies but in other neurodegenerative diseases as well. This commentary will focus on less well-acknowledged non-enzymatic functions of PREP that may provide a better approach for the development of PREP inhibitors for the treatment of neurodegenerative disorders. en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof Biochemical Pharmacology
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Neurodegeneration
dc.subject Aipha-synuclein
dc.subject Tau protein
dc.subject Amyloid-beta
dc.subject Autophagy
dc.subject Serine protease
dc.subject ACTIVE-SITE
dc.subject TAU-PROTEIN
dc.subject 317 Pharmacy
dc.title New tricks of prolyl oligopeptidase inhibitors - A common drug therapy for several neurodegenerative diseases en
dc.type Review Article
dc.contributor.organization Regenerative pharmacology group
dc.contributor.organization PREP in neurodegenerative disorders
dc.contributor.organization Division of Pharmacology and Pharmacotherapy
dc.contributor.organization Drug Research Program
dc.contributor.organization Faculty of Pharmacy
dc.description.reviewstatus Peer reviewed
dc.relation.issn 0006-2952
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
Svarbachs_et_al_New_Tricks_for_PREP_BCP_2019.pdf 1019.Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record