Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disord...

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Published in:Cellular and molecular life sciences : CMLS Vol. 69; no. 14; pp. 2387 - 2407
Main Authors: Sorce, Silvia, Krause, Karl-Heinz, Jaquet, Vincent
Format: Journal Article
Language:English
Published: Basel Springer-Verlag 01.07.2012
SP Birkhäuser Verlag Basel
Springer Nature B.V
Subjects:
Alzheimer disease
Alzheimer's disease
Amyotrophic lateral sclerosis
Antioxidants
Autoimmune diseases
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Central nervous system
Central Nervous System Diseases - enzymology
Central Nervous System Diseases - pathology
Central Nervous System Diseases - therapy
Clinical trials
Demyelinating diseases
Demyelination
diseases
Disorders
drugs
Enzyme Inhibitors - therapeutic use
Enzymes
Humans
Immune response
Immunosuppressive agents
Life Sciences
Mental disorders
Movement disorders
Multi-Author Review
NAD(P)H oxidase
NAD(P)H oxidase (H2O2-forming)
NADP (coenzyme)
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Neurodegenerative diseases
Neurological disorders
Oxidative stress
Oxygen
Parkinson disease
Parkinson's disease
Pathology
Protein Isoforms - antagonists & inhibitors
Protein Isoforms - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
Schizophrenia
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - chemistry
Small Molecule Libraries - therapeutic use
stroke
therapeutics
Antioxidants
NOX inhibitors
Oxidative stress
Brain
Stroke
NOX NADPH oxidase
Central nervous system
Schizophrenia
Autoimmune diseases
Alzheimer
Parkinson
ISSN:1420-682X, 1420-9071, 1420-9071
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Abstract Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.
AbstractList Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.
Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologies.
Author Jaquet, Vincent
Krause, Karl-Heinz
Sorce, Silvia
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22643836$$D View this record in MEDLINE/PubMed
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Issue 14
Keywords Antioxidants
NOX inhibitors
Oxidative stress
Brain
Stroke
NOX NADPH oxidase
Central nervous system
Schizophrenia
Autoimmune diseases
Alzheimer
Parkinson
Language English
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PublicationTitle Cellular and molecular life sciences : CMLS
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SubjectTerms Alzheimer disease
Alzheimer's disease
Amyotrophic lateral sclerosis
Antioxidants
Autoimmune diseases
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Central nervous system
Central Nervous System Diseases - enzymology
Central Nervous System Diseases - pathology
Central Nervous System Diseases - therapy
Clinical trials
Demyelinating diseases
Demyelination
diseases
Disorders
drugs
Enzyme Inhibitors - therapeutic use
Enzymes
Humans
Immune response
Immunosuppressive agents
Life Sciences
Mental disorders
Movement disorders
Multi-Author Review
NAD(P)H oxidase
NAD(P)H oxidase (H2O2-forming)
NADP (coenzyme)
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Neurodegenerative diseases
Neurological disorders
Oxidative stress
Oxygen
Parkinson disease
Parkinson's disease
Pathology
Protein Isoforms - antagonists & inhibitors
Protein Isoforms - metabolism
Reactive oxygen species
Reactive Oxygen Species - metabolism
Schizophrenia
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - chemistry
Small Molecule Libraries - therapeutic use
stroke
therapeutics
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Title Targeting NOX enzymes in the central nervous system: therapeutic opportunities
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