• Alzheimer’s disease (AD)
• Huntington’s disease (HD)
• Parkinson’s disease (PD)
• gene therapy
• mitochondrial dysfunction
• neuroinflammation
• pharmacogenomics
• precision medicine
• protein misfolding

• Humans
• Alzheimer Disease/therapy
• Alzheimer Disease/metabolism
• Alzheimer Disease/genetics
• Parkinson Disease/therapy
• Parkinson Disease/genetics
• Parkinson Disease/metabolism
• Amyotrophic Lateral Sclerosis/therapy
• Amyotrophic Lateral Sclerosis/genetics
• Amyotrophic Lateral Sclerosis/metabolism
• Animals
• Neurodegenerative Diseases/therapy
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/genetics
• Drug Delivery Systems
• Gene Editing

• Alzheimer’s disease
• Huntingtin’s disease
• Mitochondria
• Motor neuron disease
• Neurodegenerative disorders
• Neurotoxicity
• Oxidative stress
• Parkinson disease
• Resveratrol

• Humans
• Antioxidants/pharmacology
• Antioxidants/therapeutic use
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/drug therapy
• Oxidative Stress/drug effects
• Animals
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/therapeutic use
• Signal Transduction/drug effects
• Reactive Oxygen Species/metabolism

• Apelin
• Huntington
• Inflammation
• Neuroprotection

• Biogenesis
• Mitochondria
• MtDNA dynamics
• Neurodegeneration
• Oxidative stress
• Therapeutics

• CAG repeat
• Huntington’s disease
• dentatorubral pallidoluysian atrophy
• pathogenesis
• polyglutamine
• protein aggregation
• protein misfolding
• spinal and bulbar muscular atrophy
• spinocerebellar ataxia

• Humans
• Peptides/metabolism
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/genetics
• Animals
• Huntington Disease/genetics
• Huntington Disease/metabolism

• NRF2
• anti-oxidative therapy
• neurodegeneration
• oxidative stress
• trinucleotide repeat expansion disorders

• CMRPG3N0341 and CMRPG3N0351 Chang Gung Medical Foundation

• AD
• ALS
• GPX4
• Lipid peroxidation
• Neurodegeneration
• Oxidative stress
• Oxytosis/ferroptosis
• PD

• Humans
• Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism
• Ferroptosis
• Cell Death
• Oxidation-Reduction
• Neurodegenerative Diseases
• Glutathione Peroxidase/metabolism
• Glutathione/metabolism
• Lipid Peroxidation

• Ferroptosis
• Neurodegenerative diseases
• Nuclear factor E2-related factor 2 (Nrf2)
• Oxidative stress (OS)
• Regulation

• Humans
• Neurodegenerative Diseases
• NF-E2-Related Factor 2/metabolism
• Ferroptosis
• Oxidative Stress/physiology
• Antioxidants/metabolism

• 81673227 National Natural Science Foundation of China
• 2020JJ4080 Natural Science Foundation of Hunan Province

• health
• neurodegenerative diseases
• oxidative stress
• protein
• redox proteomics

• Alzheimer’s disease
• Amyotrophic lateral sclerosis
• Ferroptosis
• Huntington’s disease
• Multiple sclerosis
• Neurodegenerative diseases
• Parkinson’s disease
• Therapy

• Humans
• Neurodegenerative Diseases/metabolism
• Ferroptosis
• Alzheimer Disease/drug therapy
• Parkinson Disease/drug therapy
• Huntington Disease

• Huntington’s disease
• brain
• epi-metabolomics
• epigenetics
• integrative omics
• metabolomics

• Humans
• Brain/metabolism
• Huntington Disease/genetics
• Metabolome
• Methylation
• RNA, Transfer/biosynthesis
• Amino Acyl-tRNA Synthetases/genetics

• Mitochondrial dysfunction
• Neurodegenerative disorders
• Neuroinflammation
• Oxidative stress
• Peroxisome proliferator-activated receptor γ coactivator-1α

• Humans
• Quality of Life
• Neurodegenerative Diseases/drug therapy
• Neurodegenerative Diseases/genetics
• Transcription Factors/metabolism
• Huntington Disease/drug therapy
• Oxidative Stress
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism

• Arc
• BDNF
• CREB
• DNA damage
• Huntington

• Humans
• Huntington Disease/genetics
• Huntington Disease/metabolism
• Brain-Derived Neurotrophic Factor/genetics
• DNA Damage
• Signal Transduction
• Neuronal Plasticity

• 1191620 Fondo Nacional de Desarrollo Científico y Tecnológico
• 1141067 Fondo Nacional de Desarrollo Científico y Tecnológico

• BCL2
• BCLXL
• BDNF
• GABA-ergic neurons
• co-overexpression
• mesenchymal stem cells

• PCN-1-194/N/2/B Medical University of Silesia

• Aggregation
• Heat shock factor (HSF1)
• Heat shock proteins (Hsp)
• Huntington’s diseases (HD)
• Mitochondria

• Animals
• Huntington Disease/pathology
• Heat Shock Transcription Factors/genetics
• Heat Shock Transcription Factors/metabolism
• Neurodegenerative Diseases/genetics
• Protein Aggregates
• Heat-Shock Proteins/genetics
• Huntingtin Protein
• Disease Models, Animal
• Mammals/metabolism

• R01 NS110694 NINDS NIH HHS

• Drosophila melanogaster
• Huntington’s disease
• fullerenols
• neurodegeneration
• oxidative stress

• Animals
• Humans
• Drosophila
• Huntington Disease/drug therapy
• Huntington Disease/genetics
• Huntington Disease/metabolism
• Fullerenes/pharmacology
• Oxidative Stress
• Neurons/metabolism

• Huntington’s disease
• Nrf2
• antioxidant
• neurodegenerative disease
• oxidative stress

• Humans
• Corpus Striatum/metabolism
• Huntington Disease/drug therapy
• Huntington Disease/genetics
• Huntington Disease/metabolism
• Neurodegenerative Diseases/metabolism
• Oxidative Stress
• NF-E2-Related Factor 2

The main problem with using MSC (mesenchymal stem cells) to treat the deficient diseases of the central nervous system is the low cell survival rate after the transplant procedure and their low ability to spontaneously differentiate into functional neurons. The aim of this study was to investigate the effects of genetically modifying MSC. A co-overexpression of two genes was performed: BCLXL was supposed to increase the resistance of the cells to the toxic agents and BDNF was supposed to direct cells into the neuronal differentiation pathway. As a result, it was possible to obtain the functional overexpression of the BCLXL and BDNF genes. These cells had an increased resistance to apoptosis-inducing toxicants (staurosporine, doxorubicin and H₂O₂). At the same time, the genes of the neuronal pathway (CHAT, TPH1) were overexpressed. The genetically modified MSC increased the survival rate under toxic conditions, which increased the chance of surviving a transplant procedure. The obtained cells can be treated as neural cell progenitors, which makes them a universal material that can be used in various disease models. The production of neurotransmitters suggests that cells transplanted into the brain and subjected to the additional influence of the brain’s microenvironment, will be able to form synapses and become functional neurons.

• Biomarker potential
• Huntington’s disease
• Metabolic dysfunction
• Neurodegeneration
• Peripheral tissues
• Therapeutics

• Animals
• Corpus Striatum/metabolism
• Disease Models, Animal
• Humans
• Huntingtin Protein/genetics
• Huntington Disease/metabolism
• Neurodegenerative Diseases/metabolism

• Brains
• Grand River
• Non-target species
• Oxidative stress
• Pharmaceuticals
• Wastewater effluent

• Animals
• Antioxidants/analysis
• Birds/metabolism
• Brain/metabolism
• Environmental Monitoring
• Female
• Male
• Perches/metabolism
• Superoxide Dismutase/metabolism
• Wastewater/analysis
• Water Pollutants, Chemical/metabolism

Vitamin D insufficiency during childhood has been linked to the development of multiple sclerosis (MS), typically an adult-onset inflammatory demyelinating disease of the central nervous system (CNS). Since vitamin D was known to have immunoregulatory properties on both innate and adaptive immunity, it was hypothesized that low vitamin D resulted in aberrant immune responses and the development of MS. However, vitamin D receptors are present on many cell types, including neurons, oligodendrocytes, astrocytes and microglia, and vitamin D has profound effects on development and function of the CNS. This leads to the possibility that low vitamin D may alter the CNS in a manner that makes it vulnerable to inflammation and the development of MS. This review analysis the role of vitamin D in the immune and nervous system, and how vitamin D insufficiency in children may contribute to the development of MS.

• immune regulation
• multiple sclerosis
• neuroprotection
• oxidative stress
• vitamin D

• acid-sensing ion channel (ASIC)
• acidosis
• central nervous system
• immune cell
• ion channel
• neuroimmunology
• neuropathology

• Australian Research Council
• National Health and Medical Research Council
• University of Queensland

Nrf2 is a basic region leucine-zipper transcription factor that plays a pivotal role in the coordinated gene expression of antioxidant and detoxifying enzymes, promoting cell survival in adverse environmental or defective metabolic conditions. After synthesis, Nrf2 is arrested in the cytoplasm by the Kelch-like ECH-associated protein 1 suppressor (Keap1) leading Nrf2 to ubiquitin-dependent degradation. One Nrf2 activation mechanism relies on disconnection from the Keap1 homodimer through the oxidation of cysteine at specific sites of Keap1. Free Nrf2 enters the nucleus, dimerizes with small musculoaponeurotic fibrosarcoma proteins (sMafs), and binds to the antioxidant response element (ARE) sequence of the target genes. Since oxidative stress, next to neuroinflammation and mitochondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies, a molecular intervention into Nrf2/ARE signaling and the enhancement of the transcriptional activity of particular genes are targets for prevention or delaying the onset of age-related and inherited neurogenerative diseases. In this study, we review evidence for the Nrf2/ARE-driven pathway dysfunctions leading to various neurological pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, as well as amyotrophic lateral sclerosis, and the beneficial role of natural and synthetic molecules that are able to interact with Nrf2 to enhance its protective efficacy.

• Alzheimer’s disease
• Huntington’s disease
• Keap1
• Nrf2
• Parkinson’s disease
• amyotrophic lateral sclerosis
• neurodegenerative diseases
• neuroprotection
• oxidative stress

Cells have evolved extensive signaling mechanisms to maintain redox homeostasis. While basal levels of oxidants are critical for normal signaling, a tipping point is reached when the level of oxidant species exceed cellular antioxidant capabilities. Myriad pathological conditions are characterized by elevated oxidative stress, which can cause alterations in cellular operations and damage to cellular components including nucleic acids. Maintenance of nuclear chromatin are critically important for host survival and eukaryotic organisms possess an elaborately orchestrated response to initiate repair of such DNA damage. Recent evidence indicates links between the cellular antioxidant response, the DNA damage response (DDR), and the epigenetic status of the cell under conditions of elevated oxidative stress. In this emerging model, the cellular response to excessive oxidants may include redox sensors that regulate both the DDR and an orchestrated change to the epigenome in a tightly controlled program that both protects and regulates the nuclear genome. Herein we use sepsis as a model of an inflammatory pathophysiological condition that results in elevated oxidative stress, upregulation of the DDR, and epigenetic reprogramming of hematopoietic stem cells (HSCs) to discuss new evidence for interplay between the antioxidant response, the DNA damage response, and epigenetic status.

• DNA damage response
• ataxia telangiectasia mutated (ATM)
• epigenetic regulation
• innate immune response
• oxidative stress
• p53
• sepsis

• Alzheimer’s disease
• Nrf2 neuroprotection
• Parkinson’s disease
• mitochondria
• neurodegeneration

• 1200178 Fondo Nacional de Desarrollo Científico y Tecnológico

Neuroinflammation may contribute to the pathogenesis of Huntington’s disease, given evidence of activated microglia and elevated levels of inflammatory molecules in disease gene carriers, even those many years from symptom onset. We have shown previously that monocytes from Huntington’s disease patients are hyper-reactive to stimulation in a manner dependent on their autonomous expression of the disease-causing mutant HTT protein. To date, however, whether human microglia are similarly hyper-responsive in a cell-autonomous manner has not been determined.

Microglial-like cells were derived from human pluripotent stem cells (PSCs) expressing mutant HTT containing varying polyglutamine lengths. These included lines that are otherwise isogenic, such that any observed differences can be attributed with certainty to the disease mutation itself. Analyses by quantitative PCR and immunofluorescence microscopy respectively of key genes and protein markers were undertaken to determine whether Huntington’s disease PSCs differentiated normally to a microglial fate. The resultant cultures and their supernatants were then assessed by various biochemical assays and multiplex ELISAs for viability and responses to stimulation, including the release of pro-inflammatory cytokines and reactive oxygen species. Conditioned media were applied to PSC-derived striatal neurons, and vice versa, to determine the effects that the secretomes of each cell type might have on the other.

Human PSCs generated microglia successfully irrespective of the expression of mutant HTT. These cells, however, were hyper-reactive to stimulation in the production of pro-inflammatory cytokines such as IL-6 and TNFα. They also released elevated levels of reactive oxygen species that have neurotoxic potential. Accompanying such phenotypes, human Huntington’s disease PSC-derived microglia showed increased levels of apoptosis and were more susceptible to exogenous stress. Such stress appeared to be induced by supernatants from human PSC-derived striatal neurons expressing mutant HTT with a long polyglutamine tract.

These studies show, for the first time, that human Huntington’s disease PSC-derived microglia are hyper-reactive due to their autonomous expression of mutant HTT. This provides a cellular basis for the contribution that neuroinflammation might make to Huntington’s disease pathogenesis.

The online version contains supplementary material available at 10.1186/s12974-021-02147-6.

• Cytokines
• Huntington’s disease
• Microglia
• Neurodegeneration
• Pluripotent stem cells
• Reactive oxygen species
• Striatal neurons

• MitoQ
• SkQ
• antioxidants
• neurodegenerative disease
• resveratrol

• Huntington's disease
• mitochondrial dysfunction
• mutant huntingtin
• oxidative stress
• therapies

• Antioxidant
• Astrocytes
• Huntington's disease
• KEAP1
• NRF2
• Neurons
• zQ175

• Animals
• Antioxidants
• Astrocytes/metabolism
• Huntington Disease/drug therapy
• Huntington Disease/genetics
• Kelch-Like ECH-Associated Protein 1/genetics
• Kelch-Like ECH-Associated Protein 1/metabolism
• Mice
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• Neurons/metabolism
• Oxidative Stress
• Rats

• Nrf2 signaling
• Oxidative/inflammatory stress
• ROS metabolism
• Stroke-induced secondary neurodegeneration

• Cell Differentiation
• Humans
• NF-E2-Related Factor 2/metabolism
• Neural Stem Cells
• Neurodegenerative Diseases/drug therapy
• Oxidative Stress

Huntington’s disease (HD) is an inherited disorder caused by the polyglutamine (poly-Q) mutations of the HTT gene results in neurodegeneration characterized by chorea, loss of coordination, cognitive decline. However, HD pathogenesis is still elusive. Despite the availability of a wide range of biological data, a comprehensive understanding of HD’s mechanism from machine learning is so far unrealized, majorly due to the lack of needed data density.

To harness the knowledge of the HD pathogenesis from the expression profiles of postmortem prefrontal cortex samples of 157 HD and 157 controls, we used gene profiling ranking as the criteria to reduce the dimension to the order of magnitude of the sample size, followed by machine learning using the decision tree, rule induction, random forest, and generalized linear model.

These four Machine learning models identified 66 potential HD-contributing genes, with the cross-validated accuracy of 90.79 ± 4.57%, 89.49 ± 5.20%, 90.45 ± 4.24%, and 97.46 ± 3.26%, respectively. The identified genes enriched the gene ontology of transcriptional regulation, inflammatory response, neuron projection, and the cytoskeleton. Moreover, three genes in the cognitive, sensory, and perceptual systems were also identified.

The mutant HTT may interfere with both the expression and transport of these identified genes to promote the HD pathogenesis.

• Enrichment analysis
• Huntington’s disease
• Machine learning
• Transcriptional regulation

• DNA damage
• Huntington (disease)
• iPSC (induced pluripotent stem cell)
• mouse models of disease
• neurodegenaration
• primary neuron culture

• Aging
• Alzheimer’s disease
• Amyotrophic lateral sclerosis
• Huntington’s disease
• Parkinson’s disease

• Aged
• Humans
• Longevity/drug effects
• Longevity/physiology
• Neurodegenerative Diseases/classification
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/prevention & control
• Protective Agents/pharmacology

• R01 GM121756 NIGMS NIH HHS
• CIHR

Fuchs endothelial corneal dystrophy (FECD) is a common cause for heritable visual loss in the elderly. Since the first description of an association between FECD and common polymorphisms situated within the transcription factor 4 (TCF4) gene, genetic and molecular studies have implicated an intronic CTG trinucleotide repeat (CTG18.1) expansion as a causal variant in the majority of FECD patients. To date, several non-mutually exclusive mechanisms have been proposed that drive and/or exacerbate the onset of disease. These mechanisms include (i) TCF4 dysregulation; (ii) toxic gain-of-function from TCF4 repeat-containing RNA; (iii) toxic gain-of-function from repeat-associated non-AUG dependent (RAN) translation; and (iv) somatic instability of CTG18.1. However, the relative contribution of these proposed mechanisms in disease pathogenesis is currently unknown. In this review, we summarise research implicating the repeat expansion in disease pathogenesis, define the phenotype-genotype correlations between FECD and CTG18.1 expansion, and provide an update on research tools that are available to study FECD as a trinucleotide repeat expansion disease. Furthermore, ongoing international research efforts to develop novel CTG18.1 expansion-mediated FECD therapeutics are highlighted and we provide a forward-thinking perspective on key unanswered questions that remain in the field.

•

FECD is a common, age-related corneal dystrophy.

• CTG18.1
• FECD
• Fuchs endothelial corneal dystrophy
• RAN translation
• RNA toxicity
• Repeat-expansion
• Transcription factor 4
• Trinucleotide repeat
• Triplet repeat-mediated disease

• Fuchs' Endothelial Dystrophy/genetics
• Fuchs' Endothelial Dystrophy/pathology
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Genotype
• Humans
• Polymorphism, Genetic
• Transcription Factor 4/genetics
• Trinucleotide Repeat Expansion/genetics

• MR/S031820/1 Medical Research Council
• R01 EY026490 NEI NIH HHS
• Department of Health

Neurodegenerative diseases (NDs) represents debilitating conditions characterized by degeneration of neuronal cells in specific brain areas, causing disability and death in patients. In the pathophysiology of NDs, oxidative stress, apoptosis and neuroinflammation have a key role, as demonstrated by in vivo and in vitro models. Therefore, the use of molecules with antioxidant and anti-inflammatory activities represents a possible strategy for the treatment of NDs. Many studies demonstrated the beneficial effects of fumaric acid esters (FAEs) to counteract neuroinflammation and oxidative stress. Among these molecules, dimethyl fumarate (DMF) showed a valid therapeutic approach to slow down neurodegeneration and relieve symptoms in patients with NDs. DMF is a methyl ester of fumaric acid and acts as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation. Therefore, this review aims to examine the potential beneficial effects of DMF to counteract oxidative stress and inflammation in patients with NDs.

• Alzheimer’s disease (AD)
• Huntington’s disease (HD)
• Parkinson’s disease (PD)
• amyotrophic lateral sclerosis (ALS)
• dimethyl fumarate (DMF)
• oxidative stress (OS)

Aggregation of the misfolded proteins β-amyloid, tau, huntingtin, and α-synuclein is one of the most important steps in the pathology underlying a wide spectrum of neurodegenerative disorders, including the two most common ones—Alzheimer’s and Parkinson’s disease. Activity and toxicity of these proteins depends on the stage and form of aggregates. Excessive production of free radicals, including reactive oxygen species which lead to oxidative stress, is proven to be involved in the mechanism of pathology in most of neurodegenerative disorders. Both reactive oxygen species and misfolded proteins play a physiological role in the brain, and only deregulation in redox state and aggregation of the proteins leads to pathology. Here, we review the role of misfolded proteins in the activation of ROS production from various sources in neurons and glia. We discuss if free radicals can influence structural changes of the key toxic intermediates and describe the putative mechanisms by which oxidative stress and oligomers may cause neuronal death.

• mutant huntingtin protein
• neurodegeneration
• oxidative stress
• reactive oxygen species
• tau protein
• α-synuclein
• β-amyloid

DNA repeat expansion disorders are a group of neuromuscular and neurodegenerative diseases that arise from the inheritance of long tracts of nucleotide repetitions, located in the regulatory region, introns, or inside the coding sequence of a gene. Although loss of protein expression and/or the gain of function of its transcribed mRNA or translated product represent the major pathogenic effect of these pathologies, mitochondrial dysfunction and imbalance in redox homeostasis are reported as common features in these disorders, deeply affecting their severity and progression. In this review, we examine the role that the redox imbalance plays in the pathological mechanisms of DNA expansion disorders and the recent advances on antioxidant treatments, particularly focusing on the expression and the activity of the transcription factor NRF2, the main cellular regulator of the antioxidant response.

• DNA repeat expansion disorders
• FXTAS
• Friedreich’s ataxia
• Huntington’s disease
• NRF2
• fragile X syndrome
• myotonic dystrophy
• oxidative stress
• spinal and bulbar muscular atrophy
• spinocerebellar ataxia

• Animals
• DNA Repeat Expansion
• Humans
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/metabolism
• Oxidative Stress
• Signal Transduction

• antioxidants
• central nervous system disorders
• drug delivery
• nanomaterials

• Animals
• Antioxidants/pharmacokinetics
• Antioxidants/pharmacology
• Antioxidants/therapeutic use
• Blood-Brain Barrier/drug effects
• Central Nervous System Diseases/drug therapy
• Central Nervous System Diseases/etiology
• Clinical Trials as Topic
• Drug Delivery Systems/methods
• Humans
• Nanostructures/administration & dosage
• Nanostructures/chemistry
• Neurodegenerative Diseases/drug therapy
• Oxidative Stress
• Reactive Oxygen Species/metabolism

• 2018-0156 Fondazione Cariplo
• RF-2016-02361610 Italian Ministry of Health

• Brain
• Huntington animal model
• folic acid
• oxidative stress

• Adenosine Triphosphatases/metabolism
• Animals
• Antioxidants/pharmacology
• Cerebellum/drug effects
• Cerebellum/metabolism
• Cerebral Cortex/drug effects
• Cerebral Cortex/metabolism
• Corpus Striatum/drug effects
• Corpus Striatum/metabolism
• Dopamine/metabolism
• Folic Acid/pharmacology
• Glutathione/agonists
• Glutathione/metabolism
• Hydrogen Peroxide/antagonists & inhibitors
• Hydrogen Peroxide/metabolism
• Hydroxyindoleacetic Acid/agonists
• Hydroxyindoleacetic Acid/metabolism
• Lipid Peroxidation/drug effects
• Male
• Medulla Oblongata/drug effects
• Medulla Oblongata/metabolism
• Neuroprotective Agents/pharmacology
• Nitro Compounds/administration & dosage
• Nitro Compounds/antagonists & inhibitors
• Oxidative Stress/drug effects
• Propionates/administration & dosage
• Propionates/antagonists & inhibitors
• Rats
• Rats, Wistar

Increased reactive oxygen species production and oxidative stress have been implicated in the pathogenesis of numerous neurodegenerative conditions including among others Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and stroke. The endogenous antioxidant response pathway protects cells from oxidative stress by increasing the expression of cytoprotective enzymes and is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). In addition to regulating the expression of antioxidant genes, NRF2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. This is because mitochondrial dysfunction and neuroinflammation are features of many neurodegenerative diseases as well NRF2 has emerged as a promising therapeutic target. Here, we review evidence for a beneficial role of NRF2 in neurodegenerative conditions and the potential of specific NRF2 activators as therapeutic agents.

• bioenergetics
• dementia and neurological disorders
• neurodegenerative diseases

• Animals
• Anti-Inflammatory Agents/administration & dosage
• Anti-Inflammatory Agents/metabolism
• Antioxidants/administration & dosage
• Antioxidants/metabolism
• Drug Delivery Systems/methods
• Drug Delivery Systems/trends
• Humans
• NF-E2-Related Factor 2/antagonists & inhibitors
• NF-E2-Related Factor 2/metabolism
• Neurodegenerative Diseases/drug therapy
• Neurodegenerative Diseases/metabolism
• Oxidative Stress/drug effects
• Oxidative Stress/physiology
• Reactive Oxygen Species/metabolism

• RL5 GM118963 NIGMS NIH HHS
• TL4 GM118965 NIGMS NIH HHS
• UL1 GM118964 NIGMS NIH HHS

• Apoptosis
• Huntington’s disease
• Neuroprotection
• STAT3
• Twist1

• Huntington’s disease
• NAD+
• Nicotinamide Riboside
• PARPs
• PGC-1 alpha
• Sirtruins

• Animals
• Humans
• Mitochondria/metabolism
• NAD/metabolism
• Neurodegenerative Diseases/metabolism
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
• Poly (ADP-Ribose) Polymerase-1/metabolism
• Sirtuins/metabolism

• R01 NS086746 NINDS NIH HHS
• 5R01NS086746-04 NINDS NIH HHS

• Atlas
• Automated segmentation
• QSM
• SWI
• Susceptibility quantification

• Adult
• Aged
• Atlases as Topic
• Brain/anatomy & histology
• Brain/physiology
• Brain Mapping/methods
• Datasets as Topic
• Female
• Gray Matter/anatomy & histology
• Gray Matter/physiology
• Humans
• Image Processing, Computer-Assisted/methods
• Male
• Middle Aged

• P41 EB015909 NIBIB NIH HHS
• R01 NS084957 NINDS NIH HHS
• R21 AG061668 NIA NIH HHS
• R56 AG063842 NIA NIH HHS