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  • Why not I find this Research Overview earlier?

    2007-11-30

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    http://rosmarino.blogbus.com/logs/11315325.html

    That's what I want and what I should exert myself to acquire.

    Key Words & Career Goal： 

    Alzheimer，mitochondrial, neurodegeneration, G-protein coupled receptors, cell death and survival

    The primary focus of our research group is on the molecular mechanisms of neurodegeneration with an emphasis on the role of mitochondrial dysfunction. We have a longstanding interest in the pathogenic processes in Huntington’s disease and Alzheimer’s disease, and more recently in stroke.  For our studies we use a wide variety of different approaches from in vitro enzyme assays with purified proteins, to studies in whole animals.  This broad-based approach allows us to translate what we learn about a process or signaling pathway at the molecular level to the in vivo situation.  Each of the 3 areas of research that are ongoing in our lab is discussed briefly below.

    Two hallmarks of the Alzheimer’s disease brain are the intracellular neurofibrillary tangles composed primarily of the protein tau in a pathologically modified state and the extracellular senile plaques composed primarily of the Aβ peptide.  There is compelling evidence that aberrant posttranslational processing of tau is central to the disease process. Nonetheless, the upstream events that result in pathological changes in tau and the downstream mediators of the cell death processes in Alzheimer’s disease have not been fully elucidated. Therefore a major focus in our lab is first to understand the signaling cascades that are dysregulated in Alzheimer’s disease brain and result in tau pathology, and second to identify the downstream targets of tau.  Currently we are investigating how abnormal phosphorylation and proteolytic processing of tau in Alzheimer’s disease may make tau “toxic”. In addition we have a strong interest in determining how tau affects mitochondrial dynamics and function as there is exciting new data suggesting that the mitochondria may be a crucial downstream target of tau and contribute to the neurodegenerative processes.

    Our lab has a well-established interest in understanding the regulation and function of transglutaminase 2 (TG2) in neuronal cell death and survival. Recently we found that TG2 in its capacity as a scaffold protein binds HIF1β, attenuates HIF signaling and protects neurons from cell death induced by oxygen and glucose deprivation (OGD).  In addition, there is data to suggest that the mitochondria play an important role in the HIF response. Further, TG2 has been shown to modulate mitochondrial function.  Therefore we are investigating how TG2 attenuates HIF signaling and protects against OGD-induced cell death and the role of mitochondria in this process.

     

    Written by Gail V.W. Johnson

    Professor of Anesthesiology and of Pharmacology and Physiology

    University of Rochester


    随机文章：

    cold 2009-11-05

    收藏到：Del.icio.us




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