Pathophysiological processes in multiple sclerosis: focus on nuclear factor erythroid-2-related factor 2 and emerging...

Area of Science:

• Neuroimmunology
• Oxidative Stress Biology

Background:

• Multiple sclerosis (MS) is a central nervous system disorder characterized by demyelination.
• Inflammation driven by reactive oxygen species (ROS) plays a significant role in MS pathogenesis.
• The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway is a key regulator of cellular defense against oxidative stress.

Purpose of the Study:

• To review the role of ROS-related inflammation in multiple sclerosis.
• To highlight the function of the Nrf2 pathway in combating ROS.
• To discuss the therapeutic potential of dimethyl fumarate (DMF) in modulating the Nrf2 pathway for MS treatment.

Main Methods:

• Review of existing literature on MS, ROS, Nrf2 pathway, and dimethyl fumarate (DMF).
• Analysis of the molecular mechanisms by which Nrf2 regulates antioxidant response genes.
• Examination of DMF's effect on Nrf2 activation and its implications in inflammatory conditions.

Main Results:

• Nrf2 activation, through binding to the antioxidant response element, enhances the transcription of ROS-protective genes.
• Dimethyl fumarate (DMF) mimics this effect by reducing Nrf2 binding to Keap1, increasing nuclear Nrf2 levels and promoting antioxidant gene transcription.
• DMF has a proven safety profile in treating psoriasis and is effective in reducing ROS-related inflammation.

Conclusions:

• The Nrf2 pathway is a critical endogenous defense mechanism against ROS-induced damage in MS.
• Dimethyl fumarate (DMF) effectively activates the Nrf2 pathway, offering a promising therapeutic strategy for MS.
• An oral DMF analog (BG-12) has been approved for relapsing-remitting MS, providing a convenient treatment alternative.