Office: 135C Schweitzer Hall
117 Schweitzer Hall
University of Missouri
Columbia, MO 65211
|BS||Seattle Pacific University||Seattle, Wash.||Chemistry/Mathematics|
|PhD||Oregon State University||Corvallis, Ore.||Biochemistry|
An important goal for this laboratory is to investigate malfunctioning of central nervous system signaling pathways associated with neurodegenerative diseases.
The central nervous system (CNS) is comprised of complex cellular networks consisting of neurons and glial cells. Intricate biochemical pathways are known to mediate communications among these cells. Neurons and glial cells are active in their response to numerous extracellular signals, including neurotransmitters and growth factors, which are transmitted through activation of cell specific receptors and signaling pathways. Abnormal functioning of these signaling pathways can impart on a number of neurodegenerative diseases, including Alzheimer's disease, alcoholism and stroke. An important goal for this laboratory is to investigate the signaling pathways mediated by different types of receptors, especially the metabotropic G-protein-coupled receptors (GPCR) and the ionotropic receptors, associated with generation of second messengers and mobilization of intracellular calcium. Current studies in this laboratory are focused on relating these pathways to activation of phospholipases A2 (PLA2), a group of enzymes important in mediating the release of arachidonic acid and biosynthesis of prostaglandins. Increases in pro-inflammatory cytokines and oxidative stress have been regarded important pathological landmarks of many neurodegenerative diseases. One of our goals is to understand how oxidative mechanisms lead to activation of PLA2 and cyclooxygenase (COX) in neuron and glial cells and the significance of these pathways on Alzheimer's disease pathology and stroke. Cell and animal models will be used to investigate possible anti-inflammatory and anti-oxidant effects of a variety of botanical compounds. Research in this laboratory also uses animal models to examine whether nutritional supplement of these compounds may elicit neuroprotective effects. Our studies will employ basic biochemical as well as modern molecular techniques to examine gene and protein expressions. We believe that our effort to better understand the molecular mechanisms underlying signal transduction pathways will contribute to new therapeutic strategies for combating neuronal damage due to stroke, alcoholism and Alzheimer's disease.
Chuang, D. Y., A. Simonyi, Sun GY, et al. "Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2." Neuromolecular Med (2016).
Sun, GY, Li, R., Cui, J., Hannink, M., Gu, Z., Fritsche, K. L., et al. Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells. Neuromolecular Med (2016).
Ajit, D., Simonyi, A., Li, R., Chen, Z., Hannink, M., Fritsche, K. L., Sun GY et al. Phytochemicals and botanical extracts regulate NF-kappaB and Nrf2/ARE reporter activities in DI TNC1 astrocytes. Neurochem Int. 97: 49-56 (2016).
Chuang, D. Y., Simonyi, A., Kotzbauer, P. T., Gu, Z., & Sun, GY. Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway. J Neuroinflammation, 12, 199. Epub 2015/11/02 (2015).
Sun GY, Chen Z, Jasmer KJ, Chuang DY, Gu Z, Hannink M, et al. Quercetin attenuates inflammatory responses in BV-2 microglial cells: Role of MAPKs on the Nrf2 pathway and induction of heme oxygenase-1. PloS one. 2015;10(10):e0141509. Epub 2015/10/28 (2015).
Simonyi, A., Chen Z, Jiang J, Zong Y, Chuang DY, Gu Z, Lu CH, Fritsche K, Greenlief M, Rottinghaus G, Thomas AL, Lubahn DB and Sun GY. Inhibition of microglial activation by elderberry extracts and its phenolic components. Life Sci 128: 30-38 (2015).
Walker, J. M., Klakotskaia, D, Ajit D, Weisman GA, Wood WG, Sun GY, Serfozo P, Simonyi A, and Schachtman TR. "Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model." J Alzheimers Dis 44(2): 561-572 (2015).
Jiang J, Chuang DY, Zong Y, Patel J, Brownstein K, Lei W, Lu C-H, Simonyi A, Gu Z, Cui J, Rottinghaus GE, Fritsche KL, Lubahn DB, Folk, WR, Sun GY. Sutherlandia frutescens ethanol extracts inhibit oxidative stress and inflammatory responses in neurons and microglial cells. PLoS One. 9(2):e89748. PMCID: PMC3934922 (2014).
Chuang DY, Chan MH, Zong Y, Sheng W, He Y, Jiang JH, Simonyi A, Gu Z, Fritsche KL, Cui J, Lee JC, Folk WR, Lubahn DB, Sun AY, Sun GY. Magnolia polyphenols attenuate oxidative-and inflammatory responses in neurons and microglial cells. J Neuroinflammation. 10:15. doi:10.1186/1742-2094-10-15 (2013).
Askarova S, Sun Z, Sun GY, Meininger GA, Lee JC. Amyloid-β Peptide on Sialyl-Lewis(X)-Selectin-Mediated Membrane Tether Mechanics at the Cerebral Endothelial Cell Surface. PLoS One. 2013 Apr 12;8(4):e60972. doi: 10.1371/journal.pone.0060972. Print 2013.
Peterson TS, Thebeau CN, Ajit D, Camden JM, Woods LT, Gibson Wood W, Petris MJ, Sun GY, Erb L, Weisman GA. P2Y2 Nucleotide Receptor Upregulation and Activation Mediates Neurite Extension in IL-1β-treated Mouse Primary Cortical Neurons. J Neurochem. 2013 Mar 30. doi: 10.1111/jnc.12252.
Chuang DY, Chan MH, Zong Y, Sheng W, He Y, Jiang JH, Simonyi A, Gu Z, Fritsche KL, Cui J, Lee JC, Folk WR, Lubahn DB, Sun AY, Sun GY. Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells. J Neuroinflammation. 2013 Jan 29;10:15. doi: 10.1186/1742-2094-10-15.
Müller WE, Eckert GP, Sun GY, Wood WG. Alzheimer's disease: new perspectives on therapeutic targets and pathways. Foreword. Mol Neurobiol. 2012 Aug;46(1):1-2. doi: 10.1007/s12035-012-8306-5.
Sheng W, Zong Y, Mohammad A, Ajit D, Cui J, Han D, Hamilton JL, Simonyi A, Sun AY, Gu Z, Hong J-S, Weisman GA, Sun GY. Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell morphology, and upregulation of p-ERK1/2, iNOS and sPLA2-IIA expression in astrocytes and microglia. J Neuroinflammation. 8:121. PMCID: PMC3206447 (2011).
Sun AY, Wang Q, Simonyi A, Sun GY. Botanical Phenolics and Neurodegeneration. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press; 2011. Chapter 15.
Sun AY, Wang Q, Simonyi A, Sun GY. Botanical phenolics and brain health. Neuromol Med. 10:259-74. PMCID: PMC2682367 (2008).