Yun Ding

Richmond VA Medical Center, Richmond, Virginia, United States

Are you Yun Ding?

Claim your profile

Publications (5)21.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Indirubin and its derivatives have been shown to possess potent inhibitory effects on cyclin-dependent protein kinase 5 and glycogen synthase kinase 3beta, two protein kinases involved in abnormal hyperphosphorylation of tau and amyloid precursor protein processing/beta-amyloid (Abeta) production. Here, we showed that systemic treatment of APP and presenilin 1 (PS1) transgenic mice, a robust Alzheimer's disease (AD) mouse model, with indirubin-3'-monoxime (IMX; 20mg/kg; 3 times weekly), for as little as 2months, significantly attenuated spatial memory deficits. This was accompanied by a marked decrease in several AD-like phenotypes, including Abeta deposition, tau hyperphosphorylation, accumulation of activated microglia and astrocytes around Abeta plaques, and loss of synaptophysin immunoreactivity. These findings suggest that IMX is a potential therapeutic agent to combat AD.
    Neurobiology of Disease 04/2010; 39(2):156-68. · 5.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The CXC chemokine CXCL12 and its cognate receptor CXCR4 play an important role in inflammation, human immunodeficiency virus (HIV) infection and cancer metastasis. The signal transduction and intracellular trafficking of CXCR4 are involved in these functions, but the underlying mechanisms remain incompletely understood. In the present study, we demonstrated that the CXCR4 formed a complex with the cytolinker protein plectin in a ligand-dependent manner in HEK293 cells stably expressing CXCR4. The glutathione-S-transferase (GST)-CXCR4 C-terminal fusion proteins co-precipitated with the full-length and the N-terminal fragments of plectin isoform 1 but not with the N-terminal deletion mutants of plectin isoform 1, thereby suggesting an interaction between the N-terminus of plectin and the C-terminus of CXCR4. This interaction was confirmed by confocal microscopic reconstructions showing co-distribution of these two proteins in the internal vesicles after ligand-induced internalization of CXCR4 in HEK293 cells stably expressing CXCR4. Knockdown of plectin with RNA interference (RNAi) significantly inhibited ligand-dependent CXCR4 internalization and attenuated CXCR4-mediated intracellular calcium mobilization and activation of extracellular signal regulated kinase 1/2 (ERK1/2). CXCL12-induced chemotaxis of HEK293 cells stably expressing CXCR4 and of Jurkat T cells was inhibited by the plectin RNAi. Moreover, CXCR4 tropic HIV-1 infection in MAGI (HeLa-CD4-LTR-Gal) cells was inhibited by the RNAi of plectin. Thus, plectin appears to interact with CXCR4 and plays an important role in CXCR4 signaling and trafficking and HIV-1 infection.
    Experimental Cell Research 03/2008; 314(3):590-602. · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chemokines and chemokine receptors, primarily found to play a role in leukocyte migration to the inflammatory sites or to second lymphoid organs, have recently been found expressed on the resident cells of the central nervous system (CNS). These proteins are important for the development of the CNS and are involved in normal brain functions such as synaptic transmission. Increasing lines of evidence have implicated an involvement for chemokines and their receptors in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), human immunodeficiency virus-associated dementia (HAD), multiple sclerosis (MS), and stroke. Specific inhibition of the biological activities of chemokine receptors could gain therapeutic benefit for these neurodegenerative disorders. In recent years, non-peptide antagonists of chemokine receptors have been disclosed and tested in relevant pharmacological models and some of these inhibitors have entered clinical trials. The aim of this review is to outline the recent progress regarding the role of chemokines and their receptors in neurodegenerative diseases and the advancements in the development of chemokine receptor inhibitors as potential therapeutic approaches for these neurodegenerative diseases.
    Current Medicinal Chemistry 02/2007; 14(23):2456-70. · 3.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The CXCR4 chemokine receptor is a G protein-coupled receptor that plays an important role in leukocyte homing, cancer metastasis, and human immunodeficiency virus infection. In response to ligand stimulation, chemokine receptors undergo endocytosis through clathrin-coated vesicle (CCV). Uncoating of CCV, a process involving heat shock cognate protein and several other proteins, is critical for fusion of CCV to endosomal compartments. The present study demonstrated that CXCR4 was associated with the 73-kDa heat shock cognate protein (Hsc73) in human embryonic kidney 293 cells in response to ligand stimulation. Truncation of the carboxyl terminal domain of CXCR4 reduced the association with Hsc73 and a glutathione S-transferase-CXCR4 carboxyl terminal fusion protein associated with Hsc73 in vitro, suggesting involvement of the carboxyl terminal domain of the receptor in the interaction. In response to ligand stimulation, CXCR4 underwent internalization and colocalization with Hsc73, but the receptor endocytosis was blocked by knockdown of Hsc73 with RNA interference. Moreover, Hsc73 knockdown significantly reduced the CXCR4-mediated chemotaxis of U87 glioma cell lines. These findings suggest that Hsc73 plays a role in chemokine receptor trafficking and the receptor-mediated chemotaxis.
    Molecular Pharmacology 05/2006; 69(4):1269-79. · 4.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal extracellular accumulations of beta-amyloid, a major component of the senile plaques, and of the excitatory amino acid glutamate are both believed to be associated with degeneration of nerve cells in the central nervous system of patients with Alzheimer's disease. The chemokine receptor CXCR2 has been shown to play a role in protecting neurons against beta-amyloid-induced injury in vitro, but it remains unclear whether CXCR2-mediated neuroprotection is affected by glutamate. We demonstrated that pretreatment of hippocampal neurons with a sublethal concentration of N-methyl-d-aspartate (NMDA) attenuated the macrophage inflammatory protein 2 (MIP2)-induced protection against beta-amyloid-induced neuronal death. The NMDA induced inhibition was blocked by (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), a noncompetitive NMDA receptor antagonist, indicating the involvement of NMDA receptors in this process. A sublethal dose of NMDA pretreatment induced CXCR2 phosphorylation, although to a lesser extent than the receptor phosphorylation induced by MIP2, and differential serine residues were involved in NMDA- and MIP2-induced CXCR2 phosphorylation. Moreover, NMDA treatment reduced the CXCR2-mediated Ca(2+) mobilization, suggesting that NMDA induces cross-desensitization of CXCR2. CXCR2 underwent dephosphorylation after removal of the extracellular ligand, but the dephosphorylation rate was significantly reduced in the cells pretreated with NMDA. Treatment of the neuronal cells with NMDA retarded the recycling of CXCR2. In view of the critical role of receptor phosphorylation and recycling in the functional responsiveness of the chemokine receptor, these observations indicate a novel pathway through which glutamate may interfere with the neuroprotective function of chemokines.
    Molecular Pharmacology 09/2005; 68(2):528-37. · 4.41 Impact Factor

Publication Stats

66 Citations
21.72 Total Impact Points

Institutions

  • 2010
    • Richmond VA Medical Center
      Richmond, Virginia, United States
  • 2008
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • United States Department of Veterans Affairs
      Bedford, Massachusetts, United States
  • 2005–2007
    • Meharry Medical College
      • Department of Pharmacology
      Nashville, Tennessee, United States
  • 2006
    • Northeast Institute of Geography and Agroecology
      • Institute of Health Sciences
      Beijing, Beijing Shi, China