My 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.
Key techniques: behavioural studies, qPCR, reporter gene assays etc.
Research system/organism: Mus musculus
- 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.