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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Discovery and characterization of a putrescine oxidase from Rhodococcus erythropolis NCIMB 11540.
Erik W. van Hellemond,Marianne van Dijk,Dominic P. H. M. Heuts,Dick B. Janssen,Marco W. Fraaije +4 more
TL;DR: A gene encoding a putrescine oxidase (PuORh, EC 1.4.3.10) was identified from the genome of Rhodococcus erythropolis NCIMB 11540 and a model structure of PuORh was constructed, which hinted to a crucial role of Glu324 for substrate binding.
Journal ArticleDOI
Sexual dimorphic effect in the genetic association of monoamine oxidase A (MAOA) markers with autism spectrum disorder.
Deepak Verma,Barnali Chakraborti,Arijit Karmakar,Tirthankar Bandyopadhyay,Asem Surindro Singh,Swagata Sinha,Anindita Chatterjee,Saurabh Ghosh,Kochupurackal P. Mohanakumar,Kanchan Mukhopadhyay,Usha Rajamma +10 more
TL;DR: Overall results of this study identify MAOA as a possible ASD susceptibility locus and the differential genetic effect in males and females might contribute to the sex ratio differences and molecular pathology of the disorder.
Journal ArticleDOI
Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia.
TL;DR: MAOB seems to fit the ancestral susceptibility model, validating a new strategy to search for common schizophrenia susceptibility genes by focusing in those functional candidate genes subject to recent positive selection.
Journal ArticleDOI
Contilisant, a Tetratarget Small Molecule for Alzheimer's Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile.
Oscar M. Bautista-Aguilera,Josiane Budni,Francielle Mina,Eduarda Behenck Medeiros,Winnie Deuther-Conrad,Jose-Manuel Entrena,Ignacio Moraleda,Isabel Iriepa,Francisco López-Muñoz,José Marco-Contelles +9 more
TL;DR: Contilisant is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, and it significantly restores the cognitive deficit induced by Aβ1-42 in the radial maze assay in an in vivo Alzheimer's disease test.
Journal ArticleDOI
Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana)
Narayan D. Chaurasiya,Jianping Zhao,Pankaj Pandey,Robert J. Doerksen,Ilias Muhammad,Babu L. Tekwani +5 more
TL;DR: The investigation of the constituents that were isolated from Turnera diffusa for their inhibitory activities against recombinant human monoamine oxidases in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B, suggesting further investigations on acacet in 7- methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson's disease.
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.