Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of an array of enzymes with important detoxifying and antioxidant functions. Current findings support the role of high levels of oxidative stress in the pathogenesis of neurological disorders. Given the central role played by Nrf2 in counteracting oxidative damage, a number of studies have targeted the modulation of this transcription factor in order to confer neuroprotection. Nrf2 activity is tightly regulated by oxidative stress and energy-based stimuli. Thus, many dietary interventions based on energy intake regulation, such as dietary energy restriction (DER) or high-fat diet (HFD), modulate Nrf2 with consequences for a variety of cellular processes that affect brain health. DER, by either restricting calorie intake or meal frequency, activates Nrf2 thereby triggering its protective effects, whilst HFD inhibit this pathway, thereby exacerbating oxidative stress. Consequently, DER protocols can be valuable strategies in the management of central nervous system (CNS) disorders. Herein, we review current knowledge of the role of Nrf2 signaling in neurological diseases, namely Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and cerebral ischemia, as well as the potential of energy intake regulation in the management of Nrf2 signaling.

Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective

“…High levels of free radicals are neurotoxic leading to pathological processes and cell death in time. Oxidative stress has been associated with neuronal death and involved in the pathogenesis of multiple chronic neurodegenerative diseases including Alzheimer's disease, PD, Huntington's disease, amyotrophic lateral sclerosis, and neurological illnesses [55,56]. The nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE) is a key in the Nrf2 antioxidant system pathway upregulating an array of antioxidant and detoxifying enzymes.…”

“…The nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE) is a key in the Nrf2 antioxidant system pathway upregulating an array of antioxidant and detoxifying enzymes. Currently, as Nrf2 is considered a possible therapeutic target for treating oxidative stress-related disorders, some studies have targeted Nrf2 to confer neuroprotection in PD [55,56]. The Nrf2 factor counteracted PD-related neuronal cell death through the expression of cytoprotective genes with anti-inflammatory and antioxidant properties.…”

Succination of Protein Thiols in Human Brain Aging

“…Nrf2 is a transcriptional factor that acts as master regulator of the cell antioxidant defenses and the mitochondrial function in order to maintain and adapt redox homeostasis of neuronal and glial cells (Dinkova-Kostova and Abramov, 2015;Johnson and Johnson, 2015;Yamazaki et al, 2015;Baxter and Hardingham, 2016;Vasconcelos et al, 2019). Nrf2 modulates the expression of more than 200 genes by binding to a promoter element called ARE (antioxidant response element) present in these genes.…”

Influence of Nrf2 Transcription Factor Inducers on the Development of Oxidative-Nitrosative Stress in the Tissue of Cerebral Hemispheres in Rats after Modeled Traumatic Brain Injury

“…Транскрипційний фактор Nrf2 нині розглядається як чинник стійкості клітин до дії прооксидантів, який через елементи антиоксидантної відповіді в межах регуляторної області багатьох (понад 500) генів-мішеней (ARE) координує процеси антиоксидантної дії та детоксикації, дозволяючи всім типам клітин нервової системи адаптуватися до патологічних змін, викликаних внутрішньоклітинними або позаклітинними подразниками [19].…”