Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis.

Publication date: Feb 01, 2020

Multiple sclerosis (MS) is a neurologic autoimmune disorder featured by chronic inflammation of the central nervous system, demyelination and axonal damage. Recently, the term “oxinflammation” has been proposed to depict the vicious circle of chronic inflammation and oxidative stress (OS). OS promotes demyelination and neurodegeneration directly, by oxidation of lipids, proteins, and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. Many of the actors of this delicately tuned network are controlled by Keap1/Nrf2/ARE signaling pathway, a principal regulator of antioxidant and phase II detoxification genes. This pathway also has a pivotal role in inflammation, and therefore possesses a great potential in the treatment of MS. The aim of this review is to provide the newest insights in the preclinical and clinical evidence of Nrf2 induction in the regeneration of the antioxidant response and attenuation of inflammation in MS. Preclinical studies have indicated that activators of this pathway, such as epigallocatechin gallate (EGCG), curcumin, melatonin, resveratrol, and sulforaphane might be a promising therapeutic option in amelioration of MS symptoms, nevertheless, the efficacy and safety of these compounds have to be confirmed in future clinical trials.

Michalickov’a, D., Hrnc’ir, T., Canov’a, N.K., and Slanar, O. Targeting Keap1/Nrf2/ARE signaling pathway in multiple sclerosis. 20156. 2020 Eur J Pharmacol.

Concepts Keywords
Antioxidant Flavonoid
Attenuation Neuroinflammation
Autoimmune Disorder MTOR
Central Nervous System Melatonin
Clinical Trials Neurology
Curcumin Signal transduction
Demyelination Antioxidants
Detoxification Transcription factors
EGCG KEAP1
Epigallocatechin Gallate Branches of biology
Immunity Chronic inflammation
Inflammation System demyelination
Inflammatory Response Demyelination
Lipids
Melatonin
Multiple Sclerosis
Neurodegeneration
Nrf2
Oxidation
Oxidative Stress
Resveratrol
Vicious Circle

Semantics

Type Source Name
drug DRUGBANK Sulforaphane
drug DRUGBANK Resveratrol
drug DRUGBANK Melatonin
drug DRUGBANK Curcumin
drug DRUGBANK Epigallocatechin gallate
disease MESH oxidative stress
disease MESH demyelination
disease MESH inflammation
disease MESH multiple sclerosis

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