This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Approximately 2.5 million people worldwide have been diagnosed with the neurodegenerative disease multiple sclerosis (MS). Though the number of patented drugs continues to rapidly increase, effective treatments for many neural diseases remain elusive because of the complex physiologic pathways involved. Cannabinoids, bioactive compounds from the Cannabis sativa plant, have emerged as promising therapeutic agents for neuroinflammatory conditions found in diseases such as MS. The long-term goal of our work is to characterize these natural compounds as potential therapeutic options for MS and elucidate pathways through which they mediate their effects. In this project's Specific Aim 1 we use cultured glial cells as a model for testing the abilities of cannabinoid compounds?ajulemic acid and cannabidiol?to suppress markers of neuroinflammation such as nitric oxide and pro-inflammatory cytokines and chemokines. Drugs with such abilities are good candidates for treating diseases characterized by chronic neuroinflammation, such as MS. Since neurodegeneration often results from these inflammatory conditions, an ideal treatment would suppress the inflammatory response and protect surrounding neurons from damage induced by mediators of inflammation.
In Specific Aim 2, we test whether our compounds provide such protection. We induce apoptosis in cortical neurons by treatment with 2 toxic inflammatory cytokines, interferon-gamma and tumor necrosis factor-alpha), and assess effectiveness of pre-treatment with our compounds in preventing subsequent neuronal death.
In Specific Aim 3, we use cannabinoid receptor antagonists to determine whether observed anti-inflammatory and neuroprotective effects are mediated through classic CB1 and CB2 receptors. Through these proposed aims, we expect to provide the rationale for improved therapeutic options to address chronic neuroinflammation characterizing neurodegenerative diseases like MS. Characterization of the mechanisms by which the cannabinoid compounds mediate disease-modulating effects should aid the development of targeted drugs with less risk and fewer side effects than other classes of pharmaceuticals.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016460-10
Application #
8359803
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$103,822
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Allison, Devin; Delancey, Evan; Ramey, Hunter et al. (2017) Synthesis and antimicrobial studies of novel derivatives of 4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)benzoic acid as potent anti-Acinetobacter baumannii agents. Bioorg Med Chem Lett 27:387-392
MacNicol, Melanie C; Cragle, Chad E; McDaniel, F Kennedy et al. (2017) Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2. Sci Rep 7:11503
Gao, Bo; Li, Guojun; Liu, Juntao et al. (2017) Identification of driver modules in pan-cancer via coordinating coverage and exclusivity. Oncotarget 8:36115-36126
Rahmatallah, Yasir; Zybailov, Boris; Emmert-Streib, Frank et al. (2017) GSAR: Bioconductor package for Gene Set analysis in R. BMC Bioinformatics 18:61
Liu, Juntao; Li, Guojun; Chang, Zheng et al. (2016) BinPacker: Packing-Based De Novo Transcriptome Assembly from RNA-seq Data. PLoS Comput Biol 12:e1004772
Luo, Heng; Ye, Hao; Ng, Hui Wen et al. (2016) sNebula, a network-based algorithm to predict binding between human leukocyte antigens and peptides. Sci Rep 6:32115
Yu, Alexander; Demirel, Doga; Halic, Tansel et al. (2016) Virtual Intraoperative Cholangiogram Using WebCL. Stud Health Technol Inform 220:459-64
Wang, Zhenjia; Li, Guojun; Robinson, Robert W et al. (2016) UniBic: Sequential row-based biclustering algorithm for analysis of gene expression data. Sci Rep 6:23466
Rahmatallah, Yasir; Emmert-Streib, Frank; Glazko, Galina (2016) Gene set analysis approaches for RNA-seq data: performance evaluation and application guideline. Brief Bioinform 17:393-407
Beckford, Floyd A; Brock, Alyssa; Gonzalez-SarrĂ­as, Antonio et al. (2016) Cytotoxic gallium complexes containing thiosemicarbazones derived from 9-anthraldehyde: Molecular docking with biomolecules. J Mol Struct 1121:156-166

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