Targeting Nrf2/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions

Abstract

The nuclear factor erythroid 2-related factor (Nrf2) transcription factor/Hemoxygenase 1 (HO-1) is a primary regulator of essential cytoprotective responses in the brain. It activates the expression of various neuroprotective genes that code for anti-oxidant, anti-inflammatory, and detoxifying proteins. Downregulation of Nrf2/HO-1 anti-oxidant signaling is primarily responsible for developing multiple sclerosis (MS) and other neurodegenerative diseases. Downregulation of the Nrf2/HO-1 signaling pathway significantly increased oxidative stress, neuroinflammation, immune dysregulation, oligodendrocyte loss, and demyelination associated with MS-like neurocomplications. The primary goal of this review is to clarify the downregulation of Nrf2/HO-1 signaling, which may be involved in the development of MS-related neurological dysfunctions. Furthermore, the current review also identifies Nrf2/HO-1 signaling activators based on the hypothesis that restoring the dysregulated Nrf2/HO-1 anti-oxidant system could result in neuroprotection and neurotrophic effects on the clinical-pathological presentation of MS and other brain diseases. Thus, this review aims to recognize the link between the Nrf2/HO-1 anti-oxidant pathway and the development of MS-like symptoms and its prevention through the upregulation of the signaling pathway in various neurological disorders.

Keywords

• Multiple sclerosis
• Nrf2/HO-1
• Demyelination
• Oligodendrocytes
• Immune dysregulation