Abstract
Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease.
Highlights
Research from over the past 20 years has implicated the dipeptidyl peptidase (DPP) family in various physiological processes and pathologies of the immune system
We provide a comprehensive discussion and update on the roles of DPPIV, dipeptidyl peptidase II (DPPII), DPP8, DPP9, fibroblast activation protein α (FAP), prolyl oligopeptidase (PREP), and prolyl carboxypeptidase (PRCP) in the immune system and inflammatory disease
We highlight the role of these enzymes in atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease, as the DPP family encompasses possible therapeutic targets for the prevention and treatment of this disease
Summary
Research from over the past 20 years has implicated the dipeptidyl peptidase (DPP) family in various physiological processes and pathologies of the immune system. Due to similarities in substrate specificity and structural homology, it is more relevant to consider a broader family that includes prolyl oligopeptidase (PREP; EC 3.4.21.26), dipeptidyl peptidase II (DPPII) (EC 3.4.14.2), and prolyl carboxypeptidase (PRCP; EC 3.4.16.2). Due to its substrate preference for tripeptides [4], DPPII could be considered as a prolyl carboxytripeptidase, emphasizing its similarities to PRCP Another argument for considering a broader family stems from the fact that functional studies on the role of peptidases rely heavily on the use of enzyme inhibitors and many of the inhibitors used in earlier studies are known to inhibit more than one family member. Early studies on DPPIV used inhibitors which we know inhibit DPPII, DPP8, DPP9, FAP, and/or PREP due to their sequential and/or structural similarity [e.g., Ref. We highlight the role of these enzymes in atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease, as the DPP family encompasses possible therapeutic targets for the prevention and treatment of this disease
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