Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis

Thomas Philips, Andre Bento-Abreu, Annelies Nonneman, Wanda Haeck, Kim Staats, Veerle Geelen, Nicole Hersmus, Benno Küsters, Ludo Van Den Bosch, Philip Van Damme, William D. Richardson, Wim Robberecht

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


Oligodendrocytes are well known targets for immune-mediated and infectious diseases, and have been suggested to play a role in neurodegeneration. Here, we report the involvement of oligodendrocytes and their progenitor cells in the ventral grey matter of the spinal cord in amyotrophic lateral sclerosis, a neurodegenerative disease of motor neurons. Degenerative changes in oligodendrocytes were abundantly present in human patients with amyotrophic lateral sclerosis and in an amyotrophic lateral sclerosis mouse model. In the mouse model, morphological changes in grey matter oligodendrocytes became apparent before disease onset, increasingly so during disease progression, and oligodendrocytes ultimately died. This loss was compensated by increased proliferation and differentiation of oligodendrocyte precursor cells. However, these newly differentiated oligodendrocytes were dysfunctional as suggested by their reduced myelin basic protein and monocarboxylate transporter 1 expression. Mutant superoxide dismutase 1 was found to directly affect monocarboxylate transporter 1 protein expression. Our data suggest that oligodendroglial dysfunction may be a contributor to motor neuron degeneration in amyotrophic lateral sclerosis.

Original languageEnglish (US)
Pages (from-to)471-482
Number of pages12
Issue number2
StatePublished - Feb 2013
Externally publishedYes


  • ALS
  • NG2 cell
  • dysfunction
  • motor neuron disease
  • oligodendrocyte

ASJC Scopus subject areas

  • Clinical Neurology


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