Monoamine oxidase: from genes to behavior.
Jean C. Shih,K. Chen,M. J. Ridd +2 more
TLDR
MAO A and B knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders and show increased reactivity to stress.Abstract:
Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.read more
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DissertationDOI
Development of novel fluorine-18 labeled PET radioligands for monoamine oxidase B (MAO-B)
TL;DR: In vitro MAO inhibition and/or autoradiography experiments demonstrated a high selectivity for MAO-B overMAO-A for five of the compounds, which suggest that both [18F]fluorodeprenyl-D2 and [18F)fluororasagiline- D2 may be improved PET radioligands and potential molecular imaging biomarker candidates for PET studies in neuroinflammation and neurodegeneration.
Journal ArticleDOI
MAOA Gene Associated with Aggressive Behavior in Humans
Ramakrishnan,Akram Husain Rs +1 more
TL;DR: The inheritance pattern and clinically significant polymorphisms of MAOA gene has been described and the relationship between metabolomic, genetic makeup which is surrounding with the environmental factors is understood.
Journal ArticleDOI
Tautomerism of N-(3,4-dichlorophenyl)-1H-indazole-5-carboxamide - A new selective, highly potent and reversible MAO-B inhibitor
TL;DR: The tautomeric properties of an N -(3,4-dichlorophenyl)-1 H -indazole-5-carboxamide (NTZ-1006, 2 ) derivative, developed as highly potent, reversible and selective MAO-B inhibitor useful for the treatment of Parkinson's disease (PD) and other neurological disorders, have been studied both experimentally and theoretically as mentioned in this paper.
References
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Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study
Mary Sano,Christopher Ernesto,Ronald G. Thomas,Melville R. Klauber,Kimberly Schafer,Michael Grundman,Peter B. Woodbury,John H. Growdon,Carl W. Cotman,Eric Pfeiffer,Lon S. Schneider,Leon J. Thal +11 more
TL;DR: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.
Journal ArticleDOI
Some observations upon a new inhibitor of monoamine oxidase in brain tissue.
TL;DR: The hypothesis that in the enzyme prepared, the MAO is a binary system of enzymes each of which has a detectably different sensitivity to this particular inhibitor, is put forward and evidence after dialysis supports this hypothesis.
Journal ArticleDOI
Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A
TL;DR: Analytical results indicate that isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.
Journal ArticleDOI
Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA
Olivier Cases,Isabelle Seif,Joseph Grimsby,Patricia Gaspar,Kevin Chen,Sandrine Pournin,Ulrike Müller,Michel Aguet,Charles Babinet,Jean C. Shih,Edward De Maeyer +10 more
TL;DR: Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine, and adults manifested a distinct behavioral syndrome, including enhanced aggression in males.