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 Article
Comparison of Monoamine Oxidase A in Peripheral Organs in Nonsmokers and Smokers
Joanna S. Fowler,Jean Logan,Gene-Jack Wang,Nora D. Volkow,Frank Telang,Wei Zhu,Dinko Franceschi,Colleen Shea,Victor Garza,Youwen Xu,Yu-Shin Ding,David Alexoff,Donald Warner,Noelwah Netusil,Pauline Carter,Millard Jayne,Payton King,Paul Vaska +17 more
TL;DR: It is revealed that the concentration of the radiotracers in the arterial plasma is significantly lower for the smoker versus the nonsmoker and that this appears to be caused in part by retention of the Radiotracer in lungs.
Journal ArticleDOI
Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid-β aggregation for the treatment of Alzheimer's disease.
Hua-Li Yang,Pei Cai,Qiao-Hong Liu,Xue-Lian Yang,Fan Li,Jin Wang,Jia-Jia Wu,Xiao-Bing Wang,Ling-Yi Kong,Ling-Yi Kong +9 more
TL;DR: The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood- brain barrier and demonstrate that compounds 4x was an effective and promising candidate for AD therapy.
Journal ArticleDOI
Synthesis and pharmacological evaluation of novel chromone derivatives as balanced multifunctional agents against Alzheimer's disease.
TL;DR: Results suggested that s19 might be a promising multitargeted compound for AD treatment, which could reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB).
Journal ArticleDOI
Biochemical diagnosis of dopaminergic disturbances in paediatric patients: analysis of cerebrospinal fluid homovanillic acid and other biogenic amines.
Isaac Marín-Valencia,Mercedes Serrano,Aida Ormazabal,Belén Pérez-Dueñas,Angels García-Cazorla,Jaume Campistol,Rafael Artuch +6 more
TL;DR: The role played by HVA determination in CSF as a diagnostic and prognostic tool in diseases that directly or indirectly affect the dopaminergic pathway in paediatric patients is analyzed.
Journal ArticleDOI
Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements.
Annabel Whibley,Jill E. Urquhart,Jonathan K. Dore,Lionel Willatt,Georgina Parkin,Lorraine Gaunt,Graeme C.M. Black,Dian Donnai,F. Lucy Raymond +8 more
TL;DR: The clinical features accord with published reports of larger microdeletions and selective MAO-A andMAO-B deficiencies in humans and mouse models and suggest considerable functional compensation between MAO -A and MAo-B under normal conditions.
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.