Synaptic Signalling and Neurodegeneration

DZNE-Junior Research Group Synaptic Signalling and Neurodegeneration

PD Dr. Jakob von Engelhardt

Our group investigates glutamatergic synaptic transmission in the hippocampus and cortex. We are particularly interested in what role different glutamate receptors (AMPA- and NMDA receptors) and glutamate receptor-interacting proteins play in physiological and pathophysiological processes. AMPA receptors mediate most of the fast excitatory transmission in the central nervous system. NMDA receptors are important for synaptic plasticity and thus for learning and memory. In addition, excessive activation of NMDA receptors is detrimental for neurons (excitotoxicity) and contributes to the pathophysiology of brain diseases such as stroke and neurodegenerative diseases.

FUTURE OUTLOOK
1. Mechanisms of Amyloid β pathology: One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid beta-peptide (Aβ) in the brain and its deposition as plaques. However, the current prevailing view is that soluble oligomeric Aβ is one of the main mediators of Alzheimer neurotoxicity, rather than the plaques. There are indications that glutamate receptors play a role in Aβ-mediated neurotoxicity. We will use glutamate receptor transgenic mice to investigate the influence of this interaction on the physiology and anatomy of hippocampal and cortical neurons.
2. Regulation of synaptic communication via AMPA-receptor interacting proteins: Precise control of AMPA receptor number and localization on the cell membrane regulates synaptic strength and is thus of great importance for all cognitive processes. AMPA-receptor interacting proteins (TARPs, CKAMP family members, cornichons and SynDig1) regulate receptor localization and function. We will use heterologous expression systems and transgenic mice to analyze the influence of those proteins on the electrophysiological properties and localization of AMPA-receptors.

Contact

PD Dr. Jakob von Engelhardt
Synaptic Signalling and Neurodegeneration (A300)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 +49 6221 423105

Selected Publications

  • Farrow P. et al. (2015). Auxiliary subunits of the CKAMP family differentially modulate AMPA receptor properties. Elife, 4;e09693.
  • Khodosevich K. et al. (2014). Co-expressed auxiliary subunits exhibit distinct modulatory profiles on AMPA receptor function. Neuron, 83(3), 601–615.
  • Khodosevich K. et al. (2013). Connective tissue growth factor regulates interneuron survival and information processing in the olfactory bulb. Neuron, 79(6), 1136–1151.
  • von Engelhardt J. et al. (2010). CKAMP44: a brainspecific protein attenuating short-term synaptic plasticity in the dentate gyrus. Science, 327(5972), 1518–1522.
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