Related Experiment Video
Updated: Aug 11, 2025
09:02
Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
23.4K
The KEAP1-NRF2 system and neurodegenerative diseases
Akira Uruno1, Masayuki Yamamoto2
1Tohoku University, 13101, 2-1 Seiryo-cho, Aoba-ku, Sendai, Sendai, Miyagi, Japan, 980-8577; uruno@med.tohoku.ac.jp.
Antioxidants & Redox Signaling
|February 3, 2023
Summary
The KEAP1-NRF2 system regulates cellular stress responses and inflammation, making it a promising therapeutic target for neurodegenerative diseases like Alzheimer's and Parkinson's.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Central nervous system (CNS) diseases encompass neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), and multiple sclerosis (MS).
- The KEAP1-NRF2 system is a critical regulator of cellular homeostasis, protecting against oxidative stress and inflammation.
- Dysregulation of oxidative stress, inflammation, and proteostasis contributes significantly to neurodegenerative disease pathogenesis.
Purpose of the Study:
- To investigate the role of the KEAP1-NRF2 system in neurodegenerative diseases.
- To evaluate the therapeutic potential of targeting the KEAP1-NRF2 pathway for CNS disorders.
Main Methods:
- Review of existing literature on the KEAP1-NRF2 pathway and its involvement in neurodegeneration.
- Analysis of preclinical data from mouse models of neurodegenerative diseases.
- Examination of clinical data for NRF2-activating therapies.
Main Results:
- NRF2 (NF-E2-related factor 2) acts as a master regulator of antioxidant and anti-inflammatory responses.
- KEAP1 (Kelch-like ECH-associated protein 1) negatively regulates NRF2 stability and activity.
- NRF2 activation ameliorates symptoms and reduces oxidative damage and inflammation in preclinical models of neurodegenerative diseases.
- Dimethyl fumarate (DMF), an NRF2 activator, is clinically used for multiple sclerosis (MS) treatment.
Conclusions:
- The KEAP1-NRF2 system is a crucial player in maintaining CNS health and combating neuroinflammation.
- Targeting the KEAP1-NRF2 pathway represents a promising therapeutic strategy for a range of neurodegenerative diseases.
- Further research into NRF2 activators could yield novel treatments for debilitating CNS conditions.
Related Concept Videos
01:37Neural Regulation
39.6K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.6K
02:26NF-κB-dependent Signaling Pathway
7.8K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.8K
01:13The Proteasome
931
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
931
01:00Enzyme-linked Receptors
79.2K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
79.2K
01:31Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
01:15Parkinson's Disease: Overview
641
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
641