Abstract
In neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, type B monoamine oxidase (MAO-B) has been proposed to play a primary role though generating reactive oxygen species in oxidation of monoamine substrates. MAO-B oxidizes MPTP into MPP+, and an MAO-B inhibitor, deprenyl, prevents the MPTP oxidation and also MPP+neutotoxicity. These results suggest the association of MAO-B with neuronal death in neurodegenerative disorders. On the other hand, deprenyl and rasagiline, selective MAO-B inhibitors, have been proved to protect neuronal cells in cellular and animal models of neurodegeneration. These inhibitors decrease oxidation of the substrates, scavenge oxygen radicals, intervene apoptosis signal pathway in mitochondria and induce pro-survival genes coding anti-apoptotic Bcl-2 and neurotrophic factors. However, the association of MAO-B itself with the neuroprotective function of MAO-B inhibitors remains enigmatic. Recently, the involvement of type A MAO (MAO-A) in neuronal death has been shown by upregulation MAO-A expression in cellular models. MAO-A is a target of an endogenous neurotoxin, Nmethyl( R)salsolinol, and MAO-A knockdown (KO) with short interfering (si)RNA protects neuronal death from apoptosis. In addition, MAO-A mediates the increased expression of genes for anti-apoptotic, pro-survival Bcl-2 and neurotrophic factors by MAO-B inhibitors, whereas MAO-B doe not. In this review, we present our recent results on the novel role of MAO-A and MAO-B in neuronal death and also in the neuroprotective gene induction by MAO inhibitors. The future development of new series of neuroprotective drugs is discussed among compounds, which have high affinity to MAO-A and can induce pro-survival genes. MAO-A is expected to play a role in disease-modifying therapy for neurodegenerative disorders.
Keywords: Type A and B monoamine oxidase, neuroprotection, neurodegeneration, apoptosis, Bcl-2, neurotrophic factor, transcription factor, oxidative stress
Current Topics in Medicinal Chemistry
Title:Type A and B Monoamine Oxidase in Age-Related Neurodegenerative Disorders: Their Distinct Roles in Neuronal Death and Survival
Volume: 12 Issue: 20
Author(s): Makoto Naoi, Wakako Maruyama and Keiko Inaba-Hasegawa
Affiliation:
Keywords: Type A and B monoamine oxidase, neuroprotection, neurodegeneration, apoptosis, Bcl-2, neurotrophic factor, transcription factor, oxidative stress
Abstract: In neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases, type B monoamine oxidase (MAO-B) has been proposed to play a primary role though generating reactive oxygen species in oxidation of monoamine substrates. MAO-B oxidizes MPTP into MPP+, and an MAO-B inhibitor, deprenyl, prevents the MPTP oxidation and also MPP+neutotoxicity. These results suggest the association of MAO-B with neuronal death in neurodegenerative disorders. On the other hand, deprenyl and rasagiline, selective MAO-B inhibitors, have been proved to protect neuronal cells in cellular and animal models of neurodegeneration. These inhibitors decrease oxidation of the substrates, scavenge oxygen radicals, intervene apoptosis signal pathway in mitochondria and induce pro-survival genes coding anti-apoptotic Bcl-2 and neurotrophic factors. However, the association of MAO-B itself with the neuroprotective function of MAO-B inhibitors remains enigmatic. Recently, the involvement of type A MAO (MAO-A) in neuronal death has been shown by upregulation MAO-A expression in cellular models. MAO-A is a target of an endogenous neurotoxin, Nmethyl( R)salsolinol, and MAO-A knockdown (KO) with short interfering (si)RNA protects neuronal death from apoptosis. In addition, MAO-A mediates the increased expression of genes for anti-apoptotic, pro-survival Bcl-2 and neurotrophic factors by MAO-B inhibitors, whereas MAO-B doe not. In this review, we present our recent results on the novel role of MAO-A and MAO-B in neuronal death and also in the neuroprotective gene induction by MAO inhibitors. The future development of new series of neuroprotective drugs is discussed among compounds, which have high affinity to MAO-A and can induce pro-survival genes. MAO-A is expected to play a role in disease-modifying therapy for neurodegenerative disorders.
Export Options
About this article
Cite this article as:
Naoi Makoto, Maruyama Wakako and Inaba-Hasegawa Keiko, Type A and B Monoamine Oxidase in Age-Related Neurodegenerative Disorders: Their Distinct Roles in Neuronal Death and Survival, Current Topics in Medicinal Chemistry 2012; 12 (20) . https://dx.doi.org/10.2174/1568026611212200006
DOI https://dx.doi.org/10.2174/1568026611212200006 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Roles and Therapeutic Potential of Metallothioneins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Emerging Targets in Neurodegeneration: New Opportunities for Alzheimer's Disease Treatment?
Current Topics in Medicinal Chemistry Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy Enriching One’s Environment in the Face of Cognitive and Functional Loss
Current Neurovascular Research The Pathophysiology of Heme in the Brain
Current Alzheimer Research Autoantibodies Associated with Psychiatric Disorders
Current Neurovascular Research Cofilin/Actin Rod Formation by Dysregulation of Cofilin-1 Activity as a Central Initial Step in Neurodegeneration
Mini-Reviews in Medicinal Chemistry Early Expression of Neuronal Dopaminergic Markers in a Parkinson’s Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)
CNS & Neurological Disorders - Drug Targets Brain-Derived Neurotrophic Factor: A Dynamic Gatekeeper of Neural Plasticity
Current Molecular Pharmacology Linking New Paradigms in Protein Chemistry to Reversible Membrane-Protein Interactions
Current Protein & Peptide Science Synergistic Two-Way Interactions of Dietary Polyphenols and Dietary Components on the Gut Microbial Composition: Is There a Positive, Negative, or Neutralizing Effect in the Prevention and Management of Metabolic Diseases?
Current Protein & Peptide Science The Critical Role of Insulin-Like Growth Factor-1 Isoforms in the Physiopathology of Skeletal Muscle
Current Genomics Alzheimers Disease: From Pathogenesis to Disease-Modifying Approaches
CNS & Neurological Disorders - Drug Targets The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress
Current Neuropharmacology Drug Repurposing for the Treatment of Staphylococcal Infections
Current Pharmaceutical Design Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors
Current Neuropharmacology Synthesis of Novel 4-(Dimethylaminoalkyl)piperazine-1-carbodithioa t e Derivatives as Cholinesterase Inhibitors
Letters in Drug Design & Discovery Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases
Current Topics in Medicinal Chemistry Advances in Drug Delivery from Nose to Brain: An Overview
Current Drug Therapy Environmental Enrichment as a Positive Behavioral Intervention Across the Lifespan
Current Neuropharmacology