tailieunhanh - Báo cáo khoa học: ERK and cell death: ERK1⁄2 in neuronal death Srinivasa Subramaniam1 and Klaus Unsicker2

Extracellular signal-regulated kinase (ERK) is a versatile protein kinase that regulates many cellular functions. Growing evidence suggests that ERK1⁄2 plays a crucial role in promoting cell death in a variety of neuro-nal systems, including neurodegenerative diseases. | MINIREVIEW ERK and cell death ERK1 2 in neuronal death Srinivasa Subramaniam1 and Klaus Unsicker2 1 Solomon H. Snyder Department of Neuroscience Johns Hopkins University Schoolof Medicine Baltimore MD USA 2 Molecular Embryology Institute of Anatomy and CellBiology University of Freiburg Germany Keywords Akt PKB apoptosis caspase cell survival ERK ischemia neurodegenerative disease neuronal death sustained ERK transient ERK Correspondence S. Subramaniam Solomon H. Snyder Department of Neuroscience Johns Hopkins University Schoolof Medicine Baltimore MD 21205 USA Fax 410 955 3623 Tel 410 955 2379 E-mail ssubram9@ Received 19 June 2009 revised 28 August 2009 accept 4 September 2009 doi Extracellular signal-regulated kinase ERK is a versatile protein kinase that regulates many cellular functions. Growing evidence suggests that ERK1 2 plays a crucial role in promoting cell death in a variety of neuronal systems including neurodegenerative diseases. It is believed that the magnitude and the duration of ERK1 2 activity determine its cellular function. In this review we summarize recent evidence for a role of ERK1 2 in neuronal death. Furthermore we discuss the mechanisms involved in ERK1 2 mediating neuronal death. Neuronal death in the nervous system Neuronal death is a major phenomenon in nervous system development and a hallmark of all neurodegen-erative diseases. Although numerous proteins have been implicated in neuronal death the detailed mechanisms of how neurons succumb to death is far from clear. Signals for cell death can emanate from the cell surface or within the cell cytoplasm mitochondria or nucleus 1-3 . Caspases are a well-characterized group of proteins that are involved in promoting an apopto-tic mode of cell death involving DNA fragmentation and cell shrinkage. Death receptors such as tumor necrosis factor-a TNF-a on the cell surface can initiate a caspase cascade upon binding of ligands such as Fas ligand TNF-a

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