Proteases in the Nervous System

Dopamine- and cAMP-Regulated Phosphoprotein, Mr32 kDa

“…6) (Lambeir et al 2003). Although low levels of DPP4 are found in brain parenchyma, elevated activity and expression of DPP4 could be detected in the meninges, brain capillaries, choroid plexus, and circumventricular organs (CVOs) (Cynis et al 2013;Wagner et al 2015). These results imply that DPP4 is at the interphase between the CNS and the periphery via the blood circulation and CSF, respectively, thereby modulating and inactivating neuropeptides and neurotrophic growth factors (Table 1).…”

“…EM and AP form the interphase between the neuronal, endocrinal and immunological systems, involving the two stress axis hypothalamic-pituitary-adrenal (HPA) and the neurosympathico-axis (NSA). Activation of HPA and NSA results in the release of stress hormones cortisol and epinephrine, epinephrine, norepinephrine, cytokines, and NPY, which in turn interact with the brain via EM and AP and the lymph organs such as the spleen (Cynis et al 2013;Elenkov et al 2000a;Frerker et al 2009;Wagner et al 2015Wagner et al , 2016a D dendritic cells and monocytes/macrophages as well as in Kupffer-and microglia cells, where it is localized in lysosomes (Klemann et al 2016;. However, enzymatic activity of DPP4/CD26 also influence immune response, and therefore, it has not been surprising that one of the side effects of DPP4-inhibitors includes increase of infection such as SP in rhinosinusitis and angioedema, bioactive SDF-a in arthritis and NPY/PYY, as well as SP in blood pressure.…”

DOCK2; Dedicator of Cytokinesis 2

“…However, DPP4-dependent glucose-homeostasis is rather complex as insulin secretion is regulated by many DPP4-substrates, involved in the endocrine, paracrine, and neuronal systems (Fig. 6) (Lambeir et al 2003 Although low levels of DPP4 are found in brain parenchyma, elevated activity and expression of DPP4 could be detected in the meninges, brain capillaries, choroid plexus, and circumventricular organs (CVOs) (Cynis et al 2013;Wagner et al 2015). These results imply that DPP4 is at the interphase between the CNS and the periphery via the blood circulation and CSF, respectively, thereby modulating and inactivating neuropeptides and neurotrophic growth factors (Table 1).…”

Dbf4

“…EM and AP form the interphase between the neuronal, endocrinal and immunological systems, involving the two stress axis hypothalamic-pituitary-adrenal (HPA) and the neurosympathico-axis (NSA). Activation of HPA and NSA results in the release of stress hormones cortisol and epinephrine, epinephrine, norepinephrine, cytokines, and NPY, which in turn interact with the brain via EM and AP and the lymph organs such as the spleen (Cynis et al 2013;Elenkov et al 2000a;Frerker et al 2009;Wagner et al 2015Wagner et al , 2016a. NE noradrenalin, NPY neuropeptide Y, SP substance P, CVO circumventricular organ, CRH cortico-releasing hormone, ACTH Adrenocorticotropic hormone, DPP4 dipeptidyl peptidase 4, solid red arrow stimulating HPA-axis, dotted red arrows stimulating NSA, green arrows secretion by HPA (solid line) and NSA (dotted line), black arrow feedback by neuropeptides, stress hormones, cytokines or chemokine resulting in supression (dark red) or stimulation (green) D dendritic cells and monocytes/macrophages as well as in Kupffer-and microglia cells, where it is localized in lysosomes (Klemann et al 2016;.…”