will take place on Tuesday, 4 July 2017 from 17:15 to 18:15 hours in CBBM Building, Ground Floor, Room 50/51.
Host: Prof. Dr. Markus Schwaninger
Institute of Experimental and Clinical Pharmacology and Toxicology
University of Lübeck
Abstract
CD26/DP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors (Gliptins) have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients (4).
Neuropeptide Y (NPY) – a most abundant neuropeptide in the CNS and important for emotional integration and feeding regulation – represents an excellent substrate for DP4-like enzymatic activity in vivo. The bioactivity of NPY is modulated with respect to receptor selectivity via N-terminal truncation by DP4-like enzymes (5).
The presentation by Dr. von Hörsten will illustrate that DP4 and NPY form a multifunctional, highly adaptive neuro-endocrine-immune regulatory axis (1,5) and demonstrate that the activity of the DP4-NPY axis is deeply integrated various disorders of the CNS including but not limited to stress (2,7) and associated psychiatric disorders such as PTSD (6) as well as neurodegenerative disorders such as Huntington´s disease (3).
References:
- Wagner, L., Klemann, C., Stephan, M., von Horsten, S., 2016a. Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins. Clinical and experimental immunology 184, 265-283.
- Wagner, L., Kaestner, F., Wolf, R., Stiller, H., Heiser, U., Manhart, S., Hoffmann, T., Rahfeld, J.U., Demuth, H.U., Rothermundt, M., von Horsten, S., 2016b. Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation. Neuropeptides 57, 21-34.
- Wagner, L., Bjorkqvist, M., Lundh, S.H., Wolf, R., Borgel, A., Schlenzig, D., Ludwig, H.H., Rahfeld, J.U., Leavitt, B., Demuth, H.U., Petersen, A., von Horsten, S., 2016c. Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease: increased NPY levels and differential degradation of the NPY1-30 fragment. Journal of neurochemistry 137, 820-837.
- Klemann, C., Wagner, L., Stephan, M., von Horsten, S., 2016. Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system. Clinical and experimental immunology 185, 1-21.
- Wagner, L., Wolf, R., Zeitschel, U., Rossner, S., Petersen, A., Leavitt, B.R., Kastner, F., Rothermundt, M., Gartner, U.T., Gundel, D., Schlenzig, D., Frerker, N., Schade, J., Manhart, S., Rahfeld, J.U., Demuth, H.U., von Horsten, S., 2015. Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery. Journal of neurochemistry 135, 1019-1037.
- Canneva, F., Golub, Y., Distler, J., Dobner, J., Meyer, S., von Horsten, S., 2015. DPP4-deficient congenic rats display blunted stress, improved fear extinction and increased central NPY. Psychoneuroen 53, 195-206.
- Kask, A., Nguyen, H.P., Pabst, R., Von Horsten, S., 2001. Neuropeptide YY1 receptor-mediated anxiolysis in the dodsocaudal lateral septum: Functional antagonism of corticotropin-releasing hormone-induced anxiety. Neuroscience 104, 799-806.
Biosketch
Stephan von Hörsten studied medicine, history, and philosophy at Hannover Medical School (MHH) and University of Hannover, Germany (1987-1993). During that time an externship at Cardiff University (Cardiology) and a 2-year research period in Belgrade (Immunology Research Center, Lab Prof. Branislav Jankovic on Neuropharmacology and Neuroimmunology) broadened his clinical and research skills.
After working as a clinician at the Dept Clinical Immunology (1994-1996), he established a research group in Functional and Applied Anatomy at Hannover Medical School as assistant professor (W1) for "Neuro-Immune-Interactions". Research dealt with neuropeptides, peptidases, and various psychiatric, neurological, and immunological diseases. In parallel, he established a comprehensive set-up for immunological, endocrine, and behavioral phenotyping of rodents.
Since 2006 he is working as a full professor for Experimental Biomedicine at Friedrich-Alexander-University (FAU) in Erlangen, Bavaria, Germany, as Head of the Department of Experimental Therapy, Universitätsklinikum Erlangen (UKEr) and as Director of the preclinical experimental center (PETZ) at Medical Faculty, FAU. In Erlangen his research deals mainly with the generation, phenotyping, and translational research of transgenic models for aging/neurodegenerative/psychiatric disorders (transgenic rats for HD, PD, AD and SCA17) as well as novel transgenic models for AD (glutaminyl-cyclase/QC/pGluAbeta models) and Dipeptidyl-Peptidase IV (DP4/CD26) deficiency. Internationally, he is well connected with groups working on DP4-deficiency and neuropeptide Y (NPY), immune regulation, neurodegeneration (AD, HD, SCA, PD) as well as neuropsychiatric disorders.
