Peroxiredoxin 6 Alone or in Combination with Fingolimod Ameliorates EAE

Area of Science:

• Neuroimmunology
• Blood-Brain Barrier research
• Drug development for autoimmune diseases

Background:

• Multiple Sclerosis (MS) involves leukocyte infiltration and Blood-Brain Barrier (BBB) disruption.
• Some MS treatments can worsen BBB integrity as a side effect.

Purpose of the Study:

• To investigate if drugs that restore BBB function can treat MS and its model, Experimental Autoimmune Encephalomyelitis (EAE).
• To explore if these drugs can mitigate side effects of anti-lymphocytic therapies.

Main Methods:

• EAE was induced in mice.
• Disease progression, cytokine profiles, and BBB integrity were assessed.
• Effects of fingolimod and peroxiredoxin 6 (Prdx6) were evaluated.

Main Results:

• EAE mice showed neurological symptoms and BBB deterioration linked to NOX1/NOX4 upregulation.
• Fingolimod improved symptoms but caused a rebound effect upon withdrawal.
• Prdx6 ameliorated EAE, improved BBB function, and, when given before fingolimod, prevented the withdrawal effect.

Conclusions:

• Both fingolimod and Prdx6 show therapeutic potential in EAE.
• Prdx6 may be crucial for managing MS treatment side effects and preventing disease rebound.