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
More filters
Journal ArticleDOI
Genes and Aggressive Behavior: Epigenetic Mechanisms Underlying Individual Susceptibility to Aversive Environments.
TL;DR: The present review discusses data from recent research concerning the epigenetic regulation of four genes belonging to the neuroendocrine, serotonergic and oxytocinergic pathways—Nuclear receptor subfamily 3-group C-member 1 (NR3C1), oxytoc in receptor (OXTR), solute carrier-family 6 member 4 (SLC6A4) and monoamine oxidase A (MAOA)—and their role in modulating vulnerability to proactive and reactive aggressive behavior.
Journal ArticleDOI
A bioluminescent assay for monoamine oxidase activity.
Michael P. Valley,Wenhui Zhou,Erika Hawkins,John Shultz,James J. Cali,Tracy J Worzella,Laurent Bernad,Troy Good,Dave Good,Terry L. Riss,Dieter Klaubert,Keith V. Wood +11 more
TL;DR: A novel two-step homogeneous bioluminescent assay for monoamine oxidase (MAO) that is simple, sensitive, and amenable to high-throughput screening and implies that a significant number of compounds interact with the MAO enzymes and suggests that it is important to include MAO assays in drug metabolism studies.
Journal ArticleDOI
Computational Studies Applied to Flavonoids against Alzheimer's and Parkinson's Diseases.
Jéssika de Oliveira Viana,Anuraj Nayarisseri,Ernestine N T Zondegoumba,Francisco Jaime Bezerra Mendonça Junior,Marcus Tullius Scotti,Luciana Scotti +5 more
TL;DR: In silico enzymatic target studies and natural products as inhibitors for the treatment of Parkinson's and Alzheimer's diseases suggest that seven of the 39 flavonoids studied, being those with the best molecular docking results, presenting no toxicity risks, and having good absorption rates, are the flavonoid which possess the most adequate pharmacological profiles.
Journal ArticleDOI
Identification and occurrence of beta-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO).
TL;DR: The results suggest that beta-carboline alkaloids and perhaps raisins containing a high level of beta-carbolines might exhibit potential activity as MAO inhibitors, and show that some Raisin extracts and homogenates can be a source of dietary exposure to bioactive beta- carbolines.
Journal ArticleDOI
Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury.
Matteo Pardini,Frank Krueger,Frank Krueger,Colin A. Hodgkinson,Vanessa Raymont,C. Ferrier,David Goldman,Maren Strenziok,Silvia Guida,Jordan Grafman +9 more
TL;DR: Lesion location and MAO-A genotype interact in mediating aggression in PTBI and Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences.
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.