Inter- and intracellular signaling in amyotrophic lateral sclerosis: Role of p38 mitogen-activated protein kinase

C. Bendotti, M. Bao Cutrona, C. Cheroni, G. Grignaschi, D. Lo Coco, M. Peviani, M. Tortarolo, P. Veglianese, E. Zennaro

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 glial-neuron 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-specific substrates altering their physiological properties and it may turn on responsive genes leading to neurotoxicity.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalNeurodegenerative Diseases
Volume2
Issue number3-4
DOIs
Publication statusPublished - Jan 2006

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
p38 Mitogen-Activated Protein Kinases
Neuroglia
Neurons
Nerve Degeneration
Poisons
Cell Communication
Superoxides
Genes
Disease Progression
Nitric Oxide
Cytokines
Mutation

Keywords

  • Amyotrophic lateral sclerosis
  • Cytokines
  • Neuroinflammation
  • Nitric oxide
  • p38 mitogen-activated protein kinase
  • Reactive oxygen species
  • SOD1 mutants
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Inter- and intracellular signaling in amyotrophic lateral sclerosis : Role of p38 mitogen-activated protein kinase. / Bendotti, C.; Bao Cutrona, M.; Cheroni, C.; Grignaschi, G.; Lo Coco, D.; Peviani, M.; Tortarolo, M.; Veglianese, P.; Zennaro, E.

In: Neurodegenerative Diseases, Vol. 2, No. 3-4, 01.2006, p. 128-134.

Research output: Contribution to journalArticle

Bendotti, C. ; Bao Cutrona, M. ; Cheroni, C. ; Grignaschi, G. ; Lo Coco, D. ; Peviani, M. ; Tortarolo, M. ; Veglianese, P. ; Zennaro, E. / Inter- and intracellular signaling in amyotrophic lateral sclerosis : Role of p38 mitogen-activated protein kinase. In: Neurodegenerative Diseases. 2006 ; Vol. 2, No. 3-4. pp. 128-134.
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