Oligodendrocyte dysfunction in amyotrophic lateral sclerosis

Takeaway

  • Functional Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor dysregulation was identified in oligodendrocytes derived from patients with amyotrophic lateral sclerosis (ALS) and mutations in the TARDBP gene, which encodes neuronal and glial transactive response DNA binding protein 43 (TDP-43).

Why this matters

  • TDP-43 inclusions are present 95% of ALS cases, implicating a causative role of TDP-43 proteinopathy in disease pathology

  • This study is the first to examine AMPA receptor dysregulation in oligodendrocytes harboring TARDBP mutations, further implicating a key role of oligodendrocytes in ALS pathogenesis.