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ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

Erika Seki1, Xiaoli Guo2, Kazuhiko Namekata2

  • 1Laboratory of Molecular Pathology and Histology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Neuropathology : Official Journal of the Japanese Society of Neuropathology
|May 22, 2024
PubMed
Summary

Apoptosis signal-regulating kinase 1 (ASK1) is activated in the brains of multiple sclerosis (MS) patients, particularly in glial cells within active lesions. This suggests ASK1 may be a promising therapeutic target for MS treatment.

Keywords:
ASK1astrocyteglial activationmicroglia/macrophagemultiple sclerosis

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Area of Science:

  • Neuroimmunology
  • Cellular signaling in neurological disorders

Background:

  • Multiple sclerosis (MS) is a primary cause of neurological disability in young adults.
  • MS involves central nervous system inflammation and demyelination.
  • Apoptosis signal-regulating kinase 1 (ASK1) signaling is implicated in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.

Purpose of the Study:

  • To investigate the clinical significance of ASK1 activation in human MS.
  • To examine ASK1 activation in post-mortem brain tissue from MS patients.

Main Methods:

  • Analysis of post-mortem brain tissue from multiple sclerosis patients.
  • Immunohistochemical examination of ASK1 activation in glial cells (microglia/macrophages and astrocytes) within active lesions.

Main Results:

  • ASK1 activation was detected in both microglia/macrophages and astrocytes in active MS lesions.
  • ASK1 activation was significantly higher in astrocytes compared to microglia/macrophages.
  • These findings align with observations in EAE mouse models.

Conclusions:

  • ASK1 plays a significant role in glial cells during multiple sclerosis pathogenesis.
  • ASK1 represents a potential therapeutic target for managing MS.