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Updated: Jun 20, 2026

Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
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Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues

Published on: May 8, 2016

Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in

Mauricio F Farez1, Francisco J Quintana, Roopali Gandhi

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Nature Immunology
|August 18, 2009
PubMed

Insights

Higher levels of 15alpha-hydroxilkolestene (15-HC) are linked to secondary progressive multiple sclerosis (SPMS). Targeting the Toll-like receptor 2 (TLR2)-poly(ADP-ribose) polymerase 1 (PARP-1) pathway may offer new SPMS therapies.

Area of Science:

  • Neuroimmunology
  • Inflammatory diseases of the central nervous system

Background:

  • Multiple sclerosis (MS) progresses from a relapsing-remitting (RRMS) to a secondary progressive phase (SPMS).
  • SPMS causes significant disability with limited therapeutic options.
  • The underlying mechanisms driving SPMS progression remain largely unknown.

Purpose of the Study:

  • To investigate the role of 15alpha-hydroxilkolestene (15-HC) in SPMS pathogenesis.
  • To identify potential therapeutic targets for SPMS.

Main Methods:

  • Measured serum 15-HC concentrations in patients with RRMS and SPMS.
  • Induced experimental autoimmune encephalomyelitis (EAE) in mice to model MS.
  • Assessed the effects of 15-HC on immune cells (microglia, macrophages, astrocytes) in mice.
  • Investigated the involvement of Toll-like receptor 2 (TLR2) and poly(ADP-ribose) polymerase 1 (PARP-1) pathways.
  • Measured PARP-1 activity in monocytes from SPMS patients.
  • Evaluated the efficacy of PARP-1 inhibition in EAE mice.

Main Results:

  • Elevated serum 15-HC levels were observed in SPMS patients and in mice with progressive EAE, but not in RRMS patients.
  • 15-HC activated microglia, macrophages, and astrocytes in mice via the TLR2-PARP-1 pathway.
  • Increased PARP-1 activity was detected in monocytes of SPMS patients.
  • Inhibition of PARP-1 suppressed EAE progression in mice.

Conclusions:

  • The study identifies 15-HC as a potential biomarker for SPMS.
  • The TLR2-PARP-1 pathway is implicated in the pathogenesis of SPMS.
  • Targeting the TLR2-PARP-1 pathway represents a promising therapeutic strategy for SPMS.

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