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
Citations
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Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum).
TL;DR: Some of the central effects of kava may be mediated by MAO inhibition, and other kavalactones were evaluated as MAO inhibitors and Yangonin proved to be the most potent MAO inhibitor.
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Design, synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure.
Kai Cheng,Shiyu Li,Xiao Lv,Yongbin Tian,Haiyan Kong,Xufeng Huang,Yajun Duan,Jihong Han,Zhouling Xie,Chenzhong Liao +9 more
TL;DR: Compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50 = 3 nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide.
Journal ArticleDOI
[11C]Harmine Binding to Brain Monoamine Oxidase A: Test-Retest Properties and Noninvasive Quantification.
Francesca Zanderigo,Francesca Zanderigo,Alexandra E. D’Agostino,Nandita Joshi,Martin Schain,Dileep Kumar,Ramin V. Parsey,Christine DeLorenzo,J. John Mann,J. John Mann +9 more
TL;DR: Prospective studies using [11C]harmine are possible given its test-retest repeatability when binding is quantified using arterial blood, and an approach for binding potentials quantification in absence of a reference region was evaluated.
Journal ArticleDOI
Coumarin-Chalcone Hybrids as Inhibitors of MAO-B: Biological Activity and In Silico Studies.
Guillermo Moya-Alvarado,Osvaldo Yañez,Nicole Morales,Angélica González-González,Carlos Areche,Marco T. Núñez,Angélica Fierro,Olimpo García-Beltrán +7 more
TL;DR: Chalcocoumarins (3-cinnamoyl-2H-chromen-2-ones) as discussed by the authors have been shown to have the strongest activity in vitro, with IC50 = 0.76 ± 0.08 µM.
Journal ArticleDOI
Selected hydroxycoumarins as antioxidants in cells: physicochemical and reactive oxygen species scavenging studies
Fernanda Pérez-Cruz,Frederick A. Villamena,Gerald Zapata-Torres,Amlan Das,Colwyn A. Headley,Elias Quezada,Camilo López-Alarcón,Claudio Olea-Azar +7 more
TL;DR: In this paper, a set of seven hydroxycoumarin derivatives (1, 7) were tested to evaluate their antioxidant properties against peroxyl and hydroxyl radicals using two different assays, namely oxygen radical antioxidant capacity (ORAC) and non-catalytic Fenton system by ESR measurements.
References
More filters
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.