Dr. Vasileia Ismini Alexaki

B6: Technische Universität Dresden, Germany
Faculty of Medicine, Department of Clinical Pathobiochemistry

Position
Junior group leader

Background
Microglial cells are the resident immune cells of the Central Nervous System. Under normal conditions they exist in a quiescent state maintaining homeostasis. Upon trigger by an insult, such as a pathogen or an injury, they get activated acquiring anti-microbial and phagocytic features. Normally, the acute phase of inflammation is followed by a resolution phase, during which microglia return to a quiescent state. If resolution is perturbed, chronic inflammation may lead to neurodegeneration. Chronic neuroinflammation is a feature of many neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis.

We are exploring regulatory mechanisms of microglia-mediated neuroinflammation. The neurotrophin Neural Growth Factor (NGF) was found to negatively regulate microglial activation and reduce its glycolytic activity. In accordance, the neurosteroid dehydroepiandrosterone (DHEA) exerts similar anti-inflammatory effects through activation of the NGF receptor, TrkA. Application of small lipophilic ligands of TrkA, like DHEA, which can penetrate the BBB and selectively activate TrkA signaling in microglia, could be envisioned as a means to control innate immune responses in the CNS.

Role in EuroNeurotrophin
Main Supervisor ESR 8
Leader of WP4

Key Publications

• G. Fodelianaki,F. Lansing, P. Bhattarai, JH. Lim, M. Troullinaki, MA Zeballos, C. Mund, S. Grossklaus, T. Chavakis, VI. Alexaki Regulation of microglia-mediated neuroinflammmation by Nerve Growth factor (NGF). In preparation.
  
• Alexaki VI, Fodelianaki G, Neuwirth A, Mund C, Kourgiantaki A, Ieronimaki E, Lyroni K, Troullinaki M, Fujii C, Kanczkowski W, Ziogas A, Peitzsch M, Grossklaus S, Sönnichsen B, Gravanis A, Bornstein SR, Charalampopoulos I, Tsatsanis C, Chavakis T. DHEA inhibits acute microglia-mediated inflammation through activation of the TrkA-Akt1/2-CREB-Jmjd3 pathway. Mol Psychiatry. 2017 Sep 12. doi: 10.1038/mp.2017.167.
• Alexaki VI, May AE, Fujii C, V Ungern-Sternberg SN, Mund C, Gawaz M, Chavakis T, Seizer P. S100A9 induces monocyte/ macrophage migration via EMMPRIN. Thromb Haemost. 2017 Feb 28;117(3):636-639. doi: 10.1160/TH16-06-0434.
• Pediaditakis I, Efstathopoulos P, Prousis KC, Zervou M, Arévalo JC, Alexaki VI, Nikoletopoulou V, Karagianni E, Potamitis C, Tavernarakis N, Chavakis T, Margioris AN, Venihaki M, Calogeropoulou T, Charalampopoulos I, Gravanis A. Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid derivative, with TrkA receptors, regulating neuronal survival and differentiation. Neuropharmacology. 2016 Dec;111:266-282. doi: 10.1016/j.neuropharm.2016.09.007.
• Kanczkowski W, Alexaki VI, Tran N, Großklaus S, Zacharowski K, Martinez A, Popovics P, Block NL, Chavakis T, Schally AV, Bornstein SR. Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation. Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14801-6. doi: 10.1073/pnas.1313945110.
• Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis. PLoS Biol. 2011 Apr;9(4):e1001051. doi: 10.1371/journal.pbio.1001051.
• Charalampopoulos I, Alexaki VI, Lazaridis I, Dermitzaki E, Avlonitis N, Tsatsanis C, Calogeropoulou T, Margioris AN, Castanas E, Gravanis A. G protein-associated, specific membrane binding sites mediate the neuroprotective effect of dehydroepiandrosterone. FASEB J. 2006 Mar;20(3):577-9.
• Alexaki VI, Charalampopoulos I, Kampa M, Vassalou H, Theodoropoulos P, Stathopoulos EN, Hatzoglou A, Gravanis A, Castanas E. Estrogen exerts neuroprotective effects via membrane estrogen receptors and rapid Akt/NOS activation.FASEB J. 2004 Oct;18(13):1594-6.