Leibniz Research Alliance
Healthy Ageing

© Quelle: Dr. Anna Karpova, LIN, NPlast

Decline of cognitive functions during physiological ageing

Work in this project is based on the hypothesis that the slowly progressing impairment of the protein turnover at synaptic contact points between nerve cells contributes to the ageing-related decline of cognitive processes. This dysfunctional protein homeostasis is linked with a reduction of homeostatic and associative brain plasticity and in turn may disturb brain performance in various ways. Thus altered rates in gene expression, protein synthesis, transport or protein degradation may have pathological effects on neuronal excitability or neuron-glia communication. Based on our previous findings on molecular mechanisms of brain plasticity this project will study key aspects of neuronal and synaptic plasticity in physiologically aged nerve cells. The impact of these ageing processes for complex systems including brain slices and living organisms will be examined. In a research network with other Leibniz Institutes (FLI, FMP) we will explore ways to correct impaired homeostasis of synaptic proteins and to preserve cognitive abilities in old age.

Website of the project

Period: 1 January 2014 - 31 December 2016

Contact: Dr. Michael R. Kreutz
Leibniz Institute for Neurobiology (LIN)
Phone: +49 (0)391-6263 - 94181


Kravchick DO, Karpova A, Hrdinka M, Lopez-Rojas J, Iacobas S, Carbonell AU, Iacobas DA, Kreutz MR, Jordan BA (2016): Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity. EMBO J. 2016 35(17):1923-34. doi: doi: 10.15252/embj.<wbr />201593070

Spilker C, Nullmeier S, Grochowska KM, Schumacher A, Butnaru I, Macharadze T, Gomes GM, Yuanxiang P, Bayraktar G, Rodenstein C, Geiseler C, Kolodziej A, Lopez-Rojas J, Montag D, Angenstein F, Bär J, D'Hanis W, Roskoden T, Mikhaylova M, Budinger E, Ohl FW, Stork O, Zenclussen AC, Karpova A, Schwegler H, Kreutz MR (2016): A Jacob/Nsmf Gene Knockout Results in Hippocampal Dysplasia and Impaired BDNF Signaling in Dendritogenesis. PLoS Genet. 2016 12(3):e1005907. doi: 10.1371/journal.pgen.1005907

Dinamarca MC, Guzzetti F, Karpova A, Lim D, Mitro N, Musardo S, Mellone M, Marcello E, Stanic J, Samaddar T, Burguière A, Caldarelli A, Genazzani AA, Perroy J, Fagni L, Canonico PL, Kreutz MR, Gardoni F, Di Luca M (2016): Ring finger protein 10 is a novel synaptonuclear messenger encoding activation of NMDA receptors in hippocampus. Elife. 2016 5:e12430. doi: 10.7554/eLife.12430

Mikhaylova M, Bera S, Kobler O, Frischknecht R, Kreutz MR (2016): A Dendritic Golgi Satellite between ERGIC and Retromer. Cell Rep. 2016 14(2):189-99. doi: 10.1016/j.celrep.2015.12.024

Dieterich DC, Kreutz MR (2016): Proteomics of the Synapse--A Quantitative Approach to Neuronal Plasticity. Mol Cell Proteomics. 2016 15(2):368-81. doi: 10.1074/mcp.R115.051482

Niehues S, Bussmann J, Steffes G, Erdmann I, Köhrer C, Sun L, Wagner M, Schäfer K, Wang G, Koerdt SN, Stum M, Jaiswal S, RajBhandary UL, Thomas U, Aberle H, Burgess RW, Yang XL, Dieterich D, Storkebaum E (2015): Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases. Nat Commun. 2015 6:7520. doi: 10.1038/ncomms8520

Erdmann I, Marter K, Kobler O, Niehues S, Abele J, Müller A, Bussmann J, Storkebaum E, Ziv T, Thomas U, Dieterich DC (2015): Cell-selective labelling of proteomes in Drosophila melanogaster. Nat Commun. 2015 6:7521. doi: 10.1038/ncomms8521

Lopez-Rojas J, Heine M, Kreutz MR (2016): Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus. Sci Rep. 2016 6:21615. doi: 10.1038/srep21615

Ivanova D, Dirks A, Montenegro-Venegas C, Schöne C, Altrock WD, Marini C, Frischknecht R, Schanze D, Zenker M, Gundelfinger ED, Fejtova A (2015): Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo. EMBO J. 2015 34(8):1056-77. doi: 10.15252/embj.201488796

Schneider R, Hosy E, Kohl J, Klueva J, Choquet D, Thomas U, Voigt A, Heine M (2015): Mobility of calcium channels in the presynaptic membrane. Neuron. 2015 86(3):672-9. doi: 10.1016/j.neuron.2015.03.050

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