The Anti-Inflammatory and Anti-Oxidant Mechanisms of the Keap1/Nrf2/ARE Signaling Pathway in Chronic Diseases

Abstract

Oxidative stress is defined as an imbalance between production of free radicals and reactive metabolites or [reactive oxygen species (ROS)] and their elimination by through protective mechanisms, including (antioxidants). This Such imbalance leads to damage of cells and important biomolecules and cells, with hence posing a potential adverse impact on the whole organism. At the center of the day-to-day biological response to oxidative stress is the Kelch-like ECH-associated protein 1 (Keap1) - nuclear factor erythroid 2-related factor 2 (Nrf2)- antioxidant response elements (ARE) pathway, which regulates the transcription of many several antioxidant genes that preserve cellular homeostasis and detoxification genes that process and eliminate carcinogens and toxins before they can cause damage. The redox-sensitive signaling system Keap1/Nrf2/ARE plays a key role in the maintenance of cellular homeostasis under stress, inflammatory, carcinogenic, and pro-apoptotic conditions, which allows us to consider it as a pharmacological target. Herein, we review and discuss the recent advancements in the regulation of the Keap1/Nrf2/ARE system, and its role under physiological and pathophysiological conditions, e.g. such as in exercise, diabetes, cardiovascular diseases, cancer, neurodegenerative disorders, stroke, liver and kidney system, etc. and such.

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

“…In fact, oxidative stress is believed to activate a range of transcription factors/pathways including Nrf2, NF-κB, AP1, TP53, HIF-1α, HSF1, PPAR-γ, MAPK, FoxO, NOTCH, CREB, SCREB1, SP, β-catenin/Wnt, etc. [186][187][188][189]. Activation of these transcription factors is shown to be associated with the expression of over 500 different genes [186].…”

“…[186][187][188][189]. Activation of these transcription factors is shown to be associated with the expression of over 500 different genes [186]. They modulate the antioxidant defence network by effecting ROS-generating and antioxidant enzymes, mentioned above, which are critically important for animal adaptation to various stresses.…”

“…Table 3. Principal functions of enzymes encoded by Nrf2 target genes and involved in the antioxidant defence [186,197,[202][203][204].…”

Antioxidant properties and subchronic toxicity of the standardized extract of LAMIC, a phytomedicine prototype based on aqueous extracts from trunk bark of Lannea microcarpa Engl and K. Krause

“…Indeed, it is well know that free radical play a crucial role in the pathogenesis of several disease including pulmonary, cancer, rheumatoid, diabetes, cardiovascular diseases, atherosclerosis, hypertension, ischemia/reperfusion injury, etc [16][17][18][19][20] . Thus, the present study evaluate the LAMIC antioxidant activity by using three methods that are DPPH radical scavenging activity assay, ABTS radical cation scavenging activity assay and the FRAP assay.…”

Anti-aging and Anti-oxidation – Salmon Sperm as a Substitute for Nucleotide Sources

“…Moreover, ROS levels are critically connected to oxidative-induced inflammation and the occurrence/progression of various diseases (e.g., cardiovascular diseases, diabetes, neurodegenerative diseases, or cancers) [10,11,12,13]. Nrf2-Keap1 pathway is the main protective system against oxidative stress and electrophiles, but abnormal Nrf2 regulation may facilitate the progression of inflammation and, in turn, cancer formation [14,15]. Accordingly, certain ROS expression is correlated with aging, inflammatory response, and the occurrence of chronic diseases.…”