HSKL

Research Group "Molecular Mechanisms of Healthy Ageing and Neurodegeneration"

Research profile

Headed by PD Dr. Kristina Endres (JGU Mainz) the research group is investigating the following topics:

  1. Molecular relationships in the physiology and pathology of the neuronal aging process. Part of the research is the question of how cognitively healthy ageing ("well ageing") can be achieved. For this purpose, proteins that are characterized as longevity factors or as neuron-protective are investigated and possible resilience mechanisms are identified 1,2.
  2. Molecular mechanisms of Alzheimer's disease. The focus here is on the alpha-secretase ADAM10, which prevents the formation of senile plaques in the brain. In translational research approaches, pharmacological substances identified as inducers of alpha-secretase by cellular assays are firstly transferred to cognitive tests in Alzheimer's model mice and ultimately to the clinic 3,4. This is done in close cooperation with specialists in dementia and ageing research and the Study Centre for Mental Diseases.
  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. Currently, an important research topic is how the ENS changes in interaction with the microbiome in the aging process, in interaction with microbial metabolites 5 and in Alzheimer's dementia 6,7.

Further informations...

1Schuck 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.
2Anna Wierczeiko, David Fournier, Hristo Todorov, Susanne Klingenberg, Kristina Endres, Susanne Gerber; Decoupling of DNA Methylation Status and Gene Expression Levels in Aging Individuals. GENOMICS AND COMPUTATIONAL BIOLOGY Vol. 4 No. 2 (2018): e100040
3Endres 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.
4Reinhardt S, Stoye N, Luderer M, Kiefer F, Schmitt U, Lieb K, Endres K. Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks. Sci Rep. 2018 Jan 22;8(1):1329. doi: 10.1038/s41598-018-19577-7.
5Brand B, Stoye NM, Guilherme MDS, Nguyen VTT, Baumgaertner JC, Schüffler A, Thines E, Endres K. Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons. Molecules. 2019 Jul 30;24(15). pii: E2776. doi: 10.3390/molecules24152776.
6Brandscheid 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.
7dos Santos Guilherme M., Todorov H., Osterhof C., Möllerke A. , Cub K., Hankeln T., Gerber S. and Endres K. Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse. Front. Microbiol., 20 May 2020 doi.org/10.3389/fmicb.2020.01008.