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

• Main Authors: Shubham Upadhayay, Sidharth Mehan, Ph.D, M.Pharm
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Brain Disorders
• Subjects: Multiple sclerosis; Nrf2/HO-1; Demyelination; Oligodendrocytes; Immune dysregulation
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666459321000184

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.