Endres group

Molecular mechanisms of healthy aging and neurodegeneration

Group Leader

Group members

• M. Sc. Vu Thu Thuy Nguyen
• M. Sc. Tinh Nguyen Thi
• M. Sc. Robert Subirana
• M. Sc. Georgina Aline Rippert
• Cand. med. Laura-Malina Kapphan
• Cand. med. Miray Talha Aidincioglu
• Cand. med. Ithamar Haedo
• Cand. med. Julia Henny
• Stud. rer. nat. Dennis Schapelhouman
• Stud. rer. nat. Ledjona Fiska
• Stud. rer. nat. Isabel Ru-Yu Luley Hsieh

Associated:

• Dr. med. Johannes Piepgras (Clinician Scientist, CHA)
• Dr. med. Ann-Kathrin Lederer (Else Kröner Forschungskolleg scholarhsip)

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Short description

Our research group investigates the following topics:

1) Molecular relationships of the physiology and pathology of the neuronal aging process. On the one hand we want to understand how cognitively healthy ageing can be achieved. To this end, we investigate proteins that are characterized as longevity factors or as neuron-protective and their influence by resilience mechanisms.

2) Molecular mechanisms of Alzheimer's disease. Our focus here is on the alpha-secretase ADAM10, which prevents the formation of senile plaques in the brain. In a translational research approach, we transfer pharmacological substances, which we identify as inducers of alpha-secretase by cellular assays, first into cognitive tests in Alzheimer's model mice and finally into the clinic. We work closely together with the specialists in dementia and ageing research and the Study Centre for Mental Disorders.

3) Enteric nervous system and the microbiome. The intestine contains the largest peripheral nervous system (ENS) and can therefore serve as a surrogate for processes within the brain. The ENS is strongly influenced by the commensals of the intestine - the microbiome. We are currently investigating how the ENS interacts with the microbiome in the ageing process and in Alzheimer's dementia.

Cooperations

National: 

• Prof. Susanne Gerber, Human Genetics, Johannes Gutenberg University Mainz
• Prof. Helen May-Simera, Institute of Molecular Physiology, Johannes-Gutenberg University Mainz
• Prof. Tobias Hartmann, Experimental Neuroscience, Saarland University, Homburg/Saar
• Prof. Stefan Lichtenthaler, DZNE, Munich
• Prof. Karl-Herbert Schäfer, University of Applied Sciences Kaiserslautern and Pediatric Surgery, Mannheim-Heidelberg
• PD Dr. Andreas Schwiertz, Institute of Microecology, Herborn

International:

• Prof. Taisuke Tomita, University of Tokyo, Japan
• Dr. Louis Dwomoh, The Centre for Translational Pharmacology, University of Glasgow

Funding

• Alfons Geib Foundation for the Research of Alzheimer's Dementia
• Boehringer Ingelheim Funds
• Göhring Foundation Dementia Research
• MWG Rhineland-Palatinate
• EU

Projects

• MunaSet: EU-Projekt in Kollaboration unter Koordination der FH Kaiserslautern https://graphene-flagship.eu/focus/biomedical/munaset/
• NeurodegX: Forschungskolleg in Kollaboration mit der TU und FH Kaiserslautern (https://www.hs-kl.de/forschung/forschungsprojekte-kompetenzen/verbundvorhaben/neurodegx)
• MultiSensE: Forschungskolleg in Kollaboration mit der TU und FH Kaiserslautern (https://www.hs-kl.de/forschung/forschungsprojekte-kompetenzen/verbundvorhaben/multisense)
• SHARP-Projekt “Aging and functional decline of the enteric nervous system in Alzheimer’s disease and senescence-accelerated mouse models”, in Zusammenarbeit mit Oliver Tüscher, Peter Baumann und Sandra Schick (IMB, Mainz) (https://www.cha-mainz.de)
• SHARP-Projekt “Molecular signatures in vulnerable regions of the aging brain”, in Zusammenarbeit mit Oliver Tüscher, Susanne Gerber (Humangenetik, Mainz) und Dorothee Dormann (IMB, Mainz) (https://www.cha-mainz.de)

Key publications

• Valeri F, Endres K. How biological sex of the host shapes its gut microbiota. Front Neuroendocrinol. 2021 Apr;61:100912. doi: 10.1016/j.yfrne.2021.100912.
• Rosales Jubal E, Schwalm M, Dos Santos Guilherme M, Schuck F, Reinhardt S, Tose A, Barger Z, Roesler MK, Ruffini N, Wierczeiko A, Schmeisser MJ, Schmitt U, Endres K, Stroh A. Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease. Sci Rep. 2021 Mar 23;11(1):6649. doi: 10.1038/s41598-021-85912-0.
• Guilherme MDS, Nguyen VTT, Reinhardt C, Endres K. Impact of Gut Microbiome Manipulation in 5xFAD Mice on Alzheimer's Disease-Like Pathology. Microorganisms. 2021 Apr 13;9(4):815. doi: 10.3390/microorganisms9040815.
• Valeri F, Dos Santos Guilherme M, He F, Stoye NM, Schwiertz A, Endres K. Impact of the Age of Cecal Material Transfer Donors on Alzheimer's Disease Pathology in 5xFAD Mice. Microorganisms. 2021 Dec 9;9(12):2548. doi:10.3390/microorganisms9122548.
• Brummer T, Müller SA, Pan-Montojo F, Yoshida F, Fellgiebel A, Tomita T, Endres K, Lichtenthaler SF. NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer's disease. EMBO Mol Med. 2019 Apr;11(4):e9695. doi:10.15252/emmm.201809695.
• 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.
• Schuck F, Wolf D, Fellgiebel A, Endres K. Increase of α-Secretase ADAM10 in Platelets Along Cognitively Healthy Aging. J Alzheimers Dis. 2016;50(3):817-26. doi: 10.3233/JAD-150737.
  Endres K, Fahrenholz F, Lotz J, Hiemke C, Teipel S, Lieb K, Tüscher O, Fellgiebel A. Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin. Neurology. 2014 Nov 18;83(21):1930-5. doi:10.1212/WNL.0000000000001017.
• 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 Leuven F, Fahrenholz F. A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest. 2004 May;113(10):1456-64. doi: 10.1172/JCI20864.