Eyup Akgun, MS, PhD

Our laboratory targets chemokine-mGluR5 heteromer for treatment of neurodegenerative diseases. Neurodegenerative diseases affect a significant segment of the world’s population. A common feature associated with this group of diseases is chronic neuronal inflammation. Chemokines via their receptors play major role in this process by contributing to inflammation through increased glutamate release from astrocytes. Chronic high levels of glutamate create neurotoxicity by persistent stimulation of metabotropic glutamate-5 (mGluR5) and ionotropic (NMDA) receptors on neurons which lead to degeneration. The chemokine receptors and mGluR5 are co localized in glia as well as in neurons. Studies suggest functional cross-talk between chemokinereceptors and mGluR5 that mediates neuro-immune processes that play important roles in neuro-immuno communication. These heteromer may play an important role in neurodegeneration processes in the CNS. We develop bivalent ligands that contain antagonist phamacophores for chemokines (CCR5, CXCR4) etc. and mGluR5 for halting the progression of neurodegenerative diseases such as multiple sclerosis, Alzheimer’s, and neuroAIDS-associated dementia. The bivalent ligands are evaluated in vitro as well as in vivo using animal models.

• Award for Cancer Research - 1990 (Wesley Foundation, Kansas)
• Scientist of the Year- 1987 (Sedat Simavi Foundation, Turkey)
• Scholarship for Successful Foreign Student - 1972 (West Germany)

PubMed

1.Cataldo, G.; Erb, S. J.; Lunzer, M. M.; Luong, N.; Akgun, E.; Portoghese, P. S.; Olson, J. K.; Simone, D. A. The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward. Neuropharmacology 2019. DOI: 10.1016/j.neuropharm.2019.04.004

2.Akgun, E.; Lunzer, M. M.; Portoghese, P. S. Combined glia inhibition and opioid receptor agonism afford highly potent analgesics without tolerance. ACS Chem. Neurosci. 2019, 10, 2004-2011.

3.Dutta, R.; Lunzer, M. M.; Auger, J. L.; Akgun, E.; Portoghese, P. S.; Binstadt, B. A. A bivalent compound targeting CCR5 and the mu opioid receptor treats inflammatory arthritis pain in mice without inducing pharmacologic tolerance. Arthritis Res. Ther. 2018, 20, 154.

4.Cataldo, G.; Lunzer, M. M.; Olson, J. K.; Akgun, E.; Belcher, J. D.; Vercellotti, G. M.; Portoghese, P. S.; Simone, D. A. Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease. Pain 2018, 159, 1382-1391.

5.Peterson, C. D.; Kitto, K. F.; Akgun, E.; Lunzer, M. M.; Riedl, M. S.; Vulchanova, L.; Wilcox, G. L.; Portoghese, P. S.; Fairbanks, C. A. Bivalent ligand that activates mu opioid receptor and antagonizes mGluR5 receptor reduces neuropathic pain in mice. Pain 2017, 158, 2431-2441.