During the first few hours after ischemic stroke, neurons can be rescued by administering anti-apoptotic drugs. This represents an important therapeutic opportunity and thus there is a compelling need to develop novel, clinically effective drugs to target these processes. In searching for novel pharmacological agents for the treatment of stroke, Drs. Martins and Ferchmin discovered a cembranoid compound 4R and demonstrated its neuroprotective effect in vitro. Recently, these findings were extended with the demonstration that 4R also can function as an effective neuroprotective agent in vivo. The present application proposes to build on these exciting findings and expand our work on the mechanism of action of this drug, which represents a new class of compounds with neuroprotective effect against ischemia. The application will test the hypothesis that the neuroprotective effect of 4R involves Akt, a well known anti-apoptotic and anti-inflammatory protein. Specifically, we hypothesize that 4R promotes neuroprotection by activating Akt, which leads to an inhibition of apoptosis, and suppresses inflammation by inhibiting cytokine release. This project, led by Dr. Martins and co-mentored by Drs. Ferchmin and Ford, will contribute to the expansion of our program to translational research. At the same time, scientific interactions between Dr. Martins and other Pis in the SNRP community, whose research is more heavily focused on mechanistic approaches in basic neuroscience, will help Dr. Martins to develop mechanistic approaches in his lab and thus contribute to his professional development Thus, this project aims to advance professional development of a junior faculty from an underrepresented group who is developing a highly significant line of translational neuroscience research focused on neuroprotection against stroke. The project is designed to allow Dr. Martins to collect preliminary data for a competitive U01 type application to the National Institute of Health.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZNS1-SRB-N (03))
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Universidad Central Del Caribe
United States
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Astorga, César; Jorquera, Ramón A; Ramírez, Mauricio et al. (2016) Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca(2+) Channels. Sci Rep 6:32132
Bykhovskaia, Maria (2015) Calcium binding promotes conformational flexibility of the neuronal Ca(2+) sensor synaptotagmin. Biophys J 108:2507-20
Berríos, Verónica O; Boukli, Nawal M; Rodriguez, Jose W et al. (2015) Paraoxon and Pyridostigmine Interfere with Neural Stem Cell Differentiation. Neurochem Res 40:2091-101
Liu, Tianshu; Singh, Pankaj; Jenkins, James T et al. (2015) A continuum model of docking of synaptic vesicle to plasma membrane. J R Soc Interface 12:20141119
Vélez-Carrasco, Wanda; Green, Carol E; Catz, Paul et al. (2015) Pharmacokinetics and Metabolism of 4R-Cembranoid. PLoS One 10:e0121540
Fortoul, Nicole; Singh, Pankaj; Hui, Chung-Yuen et al. (2015) Coarse-Grained Model of SNARE-Mediated Docking. Biophys J 108:2258-69
Martins, A H; Hu, J; Xu, Z et al. (2015) Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia. Neuroscience 291:250-9
Ferchmin, P A; Pérez, Dinely; Cuadrado, Brenda L et al. (2015) Neuroprotection Against Diisopropylfluorophosphate in Acute Hippocampal Slices. Neurochem Res 40:2143-51
Ferchmin, P A; Andino, Myrna; Reyes Salaman, Rebeca et al. (2014) 4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration. Neurotoxicology 44:80-90
Vasin, Alexander; Zueva, Lidia; Torrez, Carol et al. (2014) Synapsin regulates activity-dependent outgrowth of synaptic boutons at the Drosophila neuromuscular junction. J Neurosci 34:10554-63

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