Our group is interested in molecular pathways that interfere with physiological and pathological processes of neuronal aging. One of our aims is to elucidate how healthy aging can be achieved, e.g. by using resilience mechanisms. Therefore, we analyse proteins which have been characterized as being longevity factors and/or of neuro-protective property and their potential interplay with gaining resilience. Furthermore, our research is focused on molecular mechanisms of Alzheimer’s disease, one of the major neurological diseases of the elderly. One example for this is our investigation of the alpha-secretase ADAM10, which is capable to prevent the deposition of senile, neurotoxic plaques in the brain. This enzyme has been shown to increase in cognitively healthy aging but on the contrary to be diminished in MCI (Mild cognitive impairment) or Alzheimer’s disease patients. We identified several regulators of ADAM10 by cellular screening approaches. Some of the “druggable” substances could already be successfully transferred to pre-clinical animal studies and first studies in patients. To pursue these translational trails, we closely interact with medical specialists in dementia and gerontology, the study centre of psychological diseases and behavioural scientists of our clinic as well as with external partners.
Prof. Susanne Gerber, Computational Systems Genetics Group, Johannes-Gutenberg University Mainz
Prof. Thomas Efferth, Institut für Therapeutische Lebenswissenschaften, Pharmazie, Johannes-Gutenberg University Mainz
Prof. Roland Stauber, HNO, University Medical Center, Johannes-Gutenberg Universität Mainz
Prof. Thomas Deller, Anatomy, Goethe University, Frankfurt am Main
Prof. Tobias Hartmann, Experimental Neurology, University of the Saarland, Homburg/Saar
Prof. Karl-Herbert Schäfer, University of Applied Sciences Kaiserslautern and Pediatric Surgery, Mannheim-Heidelberg
Prof. Taisuke Tomita, University of Tokyo, Japan
Prof. I. Lee, College of Pharmacy, Chonnam National University, South Korea
Alfons Geib Stiftung zur Erforschung der Alzheimer-Demenz
Boehringer Ingelheim Fonds
Göhring Stiftung Demenz-Forschung
Stiftung Innovation Rheinland-Pfalz
Endres K, Deller T. Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms. Front Mol Neurosci. 2017
Brandscheid C, Schuck F, Reinhardt S, Schäfer KH, Pietrzik CU, Grimm M, Hartmann T, Schwiertz A, Endres K. Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model. J Alzheimers Dis. 2017;56(2):775-788. doi: 10.3233/JAD-160926.
Endres, K, Fahrenholz, F, Lotz, J, Hiemke, C, Teipel, S, Lieb, K, Tüscher, O, Fellgiebel, A. Increased APPs-alpha levels in Alzheimer’s disease patients treated with acitretin. Neurology 2014 83(21): 1930-1935
Sakry, D, Neitz, A, Singh, J, Frischknecht, R, Marongiu, D, Binamé, F, Walmsley-Perera, S, Endres, K, Lutz, B, Radyushkin, K, Trotter, J, Mittmann, T. Oligodendrocyte Precursor Cells Modulate the Neuronal Network by Activity-Dependent Ectodomain Cleavage of Glial NG2. PLOS Biology 2014 12(11): e10 
Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F. Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J 2009;23(6):1643-54.
Postina R, Schroeder A, Dewachter I, Bohl J, Schmitt U, Kojro E, Prinzen C, Endres K, Hiemke C, Blessing M, Flamez P, Dequenne A, Godaux E, van LF, Fahrenholz F. A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 2004;113(10):1456-64.01993