Increased expression of endoplasmic reticulum stress-related signaling pathway molecules in multiple sclerosis lesions

Aoife Ní Mháille, Stephen McQuaid, Anthony Windebank, Paula Cunnea, Jill McMahon, Afshin Samali, Una FitzGerald

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Activation of endoplasmic reticulum (ER) stress-related cell signals has been reported in several neurologic disorders and may contribute to neurodegeneration. Endoplasmic reticulum stress is also linked to ischemic injury. However, activation of an ER stress response has not been investigated in multiple sclerosis (MS) lesions. We detected increased expression of ER stress-associated C/EBP homologous protein, immunoglobulin heavy chain-binding protein, and X-box-binding protein 1 in multiple cell types, including oligodendrocytes, astrocytes, T cells, and microglia in active MS lesions. Semiquantitative analysis of expression in active, chronic active, and chronic inactive lesions indicated that levels of immunoglobulin heavy chain-binding protein were significantly higher in acute lesions than in non-MS controls or MS normal-appearing white matter, and that ER stress-associated C/EBP homologous protein was upregulated to the greatest extent at the edges of chronic active lesions. Because demyelination may be triggered by a tissue response to ischemia-like conditions, changes in the hypoxia-related antigen D-110 were also investigated, and it was found that increased ER stress-associated C/EBP homologous protein expression can occur in either the presence or absence of D-110. A possible link between a perturbed ER and lesion development in MS suggests a signaling pathway that may represent a new therapeutic target in MS.

Original languageEnglish (US)
Pages (from-to)200-211
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Issue number3
StatePublished - Mar 2008


  • BiP
  • CHOP
  • D-110
  • Endoplasmic reticulum stress
  • Hypoxia
  • Multiple sclerosis
  • XBP1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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