Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inheritance of Alzheimer's disease in some families, as well as ablation/rescue genetics in mice, suggest that point mutations in the presenilin-1 (PS1) gene can cause disease through an unknown gain-of-function. While mutations associated with familial Alzheimer's can alter apoptotic rates and beta-amyloid precursor processing, it is possible that other physiological effects contribute to pathogenesis. We have begun to explore effects on neurotransmission by monitoring responses of the neuropotent Ntera-2 cell line expressing wild-type PS1 or a FAD mutant thereof. Although no differences were initially apparent in calcium responses of metabotropic receptors, responses to glutamate were dampened in cells expressing the L286V mutant of PS1. Analysis of ionotropic agonists demonstrated that AMPA receptor alterations were responsible for this effect, whereas NMDA responses were unaltered. These data suggest that PS1 mutation could lead to cognitive deficits through subtoxic physiological effects.
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PMID:Inhibition of AMPA responses by mutated presenilin 1. 1046 68

Spermine oxidase is a FAD-containing enzyme involved in polyamines catabolism, selectively oxidizing spermine to produce H2O2, spermidine, and 3-aminopropanal. Spermine oxidase is highly expressed in the mouse brain and plays a key role in regulating the levels of spermine, which is involved in protein synthesis, cell division and cell growth. Spermine is normally released by neurons at synaptic sites where it exerts a neuromodulatory function, by specifically interacting with different types of ion channels, and with ionotropic glutamate receptors. In order to get an insight into the neurobiological roles of spermine oxidase and spermine, we have deregulated spermine oxidase gene expression producing and characterizing the transgenic mouse model JoSMOrec, conditionally overexpressing the enzyme in the neocortex. We have investigated the effects of spermine oxidase overexpression in the mouse neocortex by transcript accumulation, immunohistochemical analysis, enzymatic assays and polyamine content in young and aged animals. Transgenic JoSMOrec mice showed in the neocortex a higher H2O2 production in respect to Wild-Type controls, indicating an increase of oxidative stress due to SMO overexpression. Moreover, the response of transgenic mice to excitotoxic brain injury, induced by kainic acid injection, was evaluated by analysing the behavioural phenotype, the immunodistribution of neural cell populations, and the ultrastructural features of neocortical neurons. Spermine oxidase overexpression and the consequently altered polyamine levels in the neocortex affects the cytoarchitecture in the adult and aging brain, as well as after neurotoxic insult. It resulted that the transgenic JoSMOrec mouse line is more sensitive to KA than Wild-Type mice, indicating an important role of spermine oxidase during excitotoxicity. These results provide novel evidences of the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain.
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PMID:A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury. 2384 Mar 6