Inter- and Intracellular Signaling in Amyotrophic Lateral Sclerosis: Role of p38 Mitogen-Activated Protein Kinase

被引:33
作者
Bendotti, C. [1 ]
Cutrona, M. Bao [1 ]
Cheroni, C. [1 ]
Grignaschi, G. [1 ]
Lo Coco, D. [1 ,2 ]
Peviani, M. [1 ]
Tortarolo, M. [1 ]
Veglianese, P. [1 ]
Zennaro, E. [1 ]
机构
[1] Mario Negri Inst Pharmacol Res, Dept Neurosci, Mol Neurobiol Lab, IT-20157 Milan, Italy
[2] Univ Palermo, Inst Neuropsychiat, ALS Clin Res Ctr, Palermo, Italy
关键词
Amyotrophic lateral sclerosis; SOD1; mutants; Tumor necrosis factor-alpha; Cytokines; Neuroinflammation; Reactive oxygen species; Nitric oxide; p38 mitogen-activated protein kinase;
D O I
10.1159/000089617
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The pathogenetic processes underlying the selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) are complex and still not completely understood even in the cases of inherited disease caused by mutations in the Cu/Zn superoxide dismutase-dependent (SOD1) gene. Recent evidence supports the view that ALS is not a cell-autonomous disease and that glialneuron cross-talk, throughout cytokines and other toxic factors like the nitric oxide and superoxide, is a crucial determinant for the induction of motor neuron death. This cell-cell interaction may determine the progression of the disease through processes that are likely independent of the initial trigger and that may converge on the activation of intracellular death pathways in the motor neurons. In this review we provide support to the hypothesis that aberrant expression and activity of p38 mitogen protein-activated kinases cascade (p38MAPK) in motor neurons and glial cells may play a role in the development and progression of ALS. Increased activation of p38MAPK may phosphorylate neuron-specifi c substrates altering their physiological properties and it may turn on responsive genes leading to neurotoxicity. Copyright (C) 2005 S. Karger AG, Basel
引用
收藏
页码:128 / 134
页数:7
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