Mechanisms of Neurodegeneration

Summary

Principal Investigator: Roger Davis
Abstract: The overall goal of this research program is to understand the mechanism of signal transduction mediated by MAP kinases in mammalian cells. A focus of this study is the c-Jun NH2-terminal kinase (JNK) group of MAP kinases. Many of the components of the JNK protein kinase cascade have been identified by molecular cloning and have been characterized in biochemical studies. However, a complete understanding of the physiological function of JNK has remained elusive. The long-term goal of this research is to define the molecular mechanisms and physiological significance of JNK activation in neurons. A specific focus of our analysis will be to determine the role of JNK in neurodegeneration. Achievement of the goals of this proposal will increase understanding of the molecular mechanism of MAP kinase signal transduction in vivo. This information represents a basis for the design of novel therapeutic strategies for the treatment of neurodegenerative diseases, including stroke. The Specific Aims of this proposal are to examine: 1. The physiological role of JNK in neurons. 2. The mechanism of JNK-induced neurodegeneration.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Multisite phosphorylation regulates Bim stability and apoptotic activity
    Anette Hübner
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Mol Cell 30:415-25. 2008
  2. pmc c-Jun NH2-terminal kinase is required for lineage-specific differentiation but not stem cell self-renewal
    Ping Xu
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Mol Cell Biol 30:1329-40. 2010
  3. pmc Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists
    Kapil Bahl
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 84:4866-77. 2010
  4. pmc cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance
    Guadalupe Sabio
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Campus de Cantoblanco, 28049 Madrid, Spain
    Trends Biochem Sci 35:490-6. 2010
  5. pmc JNK regulates FoxO-dependent autophagy in neurons
    Ping Xu
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 25:310-22. 2011

Scientific Experts

  • Roger Davis
  • Ping Xu
  • Kapil Bahl
  • Guadalupe Sabio
  • Anette Hübner
  • Judith Reilly
  • Madhumita Das
  • Raymond M Welsh
  • Anette Hüebner
  • Richard A Flavell
  • Tamera Barrett

Detail Information

Publications5

  1. pmc Multisite phosphorylation regulates Bim stability and apoptotic activity
    Anette Hübner
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Mol Cell 30:415-25. 2008
    ..Together, these data indicate that phosphorylation can regulate Bim by multiple mechanisms and that the phosphorylation of Bim on different sites can contribute to the sensitivity of cellular apoptotic responses...
  2. pmc c-Jun NH2-terminal kinase is required for lineage-specific differentiation but not stem cell self-renewal
    Ping Xu
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Mol Cell Biol 30:1329-40. 2010
    ..Together, these data demonstrate that JNK is not required for proliferation or self-renewal of ES cells, but JNK plays a key role in the differentiation of ES cells...
  3. pmc Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists
    Kapil Bahl
    Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 84:4866-77. 2010
    ..Evidence is presented showing that high levels of T cell attrition, as found in young mice, correlate with reduced immunodomination by cross-reactive memory cells...
  4. pmc cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance
    Guadalupe Sabio
    Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Campus de Cantoblanco, 28049 Madrid, Spain
    Trends Biochem Sci 35:490-6. 2010
    ..Together, these studies establish JNK1 as a potential pharmacological target for the development of drugs that might be useful for the treatment of insulin resistance, metabolic syndrome, and type 2 diabetes...
  5. pmc JNK regulates FoxO-dependent autophagy in neurons
    Ping Xu
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 25:310-22. 2011
    ..These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons...