RESUMO
Mental retardation is a progressive condition in Down syndrome: intelligence starts to decline linearly within the first year. This phenomenon could be related to the overproduction of a toxic compound, hydrogen sulfide. Indeed, a gene located on chromosome 21 controls the production of cystathionine-ß-synthase, an enzyme involved in hydrogen sulfide production in the central nervous system. It has recently been demonstrated that excess cystathionine-ß-synthase levels are needed and sufficient to induce cognitive phenotypes in mouse models of Down syndrome. Thus, two therapeutic options might be used in Down syndrome patients: the use of a specific cystathionine ß-synthase inhibitor and the use of an effective antidote to reduce hydrogen sulfide toxicity. Prenatal treatment of Down syndrome fetuses is also suggested.
Assuntos
Cistationina beta-Sintase/fisiologia , Síndrome de Down/psicologia , Sulfeto de Hidrogênio/antagonistas & inibidores , Deficiência Intelectual/terapia , Ácido Amino-Oxiacético/uso terapêutico , Animais , Benserazida/uso terapêutico , Encéfalo/metabolismo , Cromossomos Humanos Par 21/genética , Cobamidas/uso terapêutico , Cistationina beta-Sintase/antagonistas & inibidores , Cistationina beta-Sintase/genética , Modelos Animais de Doenças , Progressão da Doença , Dissulfiram/uso terapêutico , Síndrome de Down/genética , Inibidores Enzimáticos/uso terapêutico , Dosagem de Genes , Humanos , Sulfeto de Hidrogênio/metabolismo , Recém-Nascido , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/genética , Camundongos , Mitocôndrias/metabolismo , Ratos , Nitrito de Sódio/uso terapêutico , Especificidade da Espécie , Tiossulfatos/metabolismoRESUMO
Respiratory failure leads to tissue hypoxia and subsequent organ damage. The crocodile hemoglobin affinity for oxygen is significantly reduced in the presence of CO2, allowing crocodiles to stay under water for more than 1h. The crocodile bicarbonate effect can possibly be transplanted into the human hemoglobin by replacing only five and seven amino acid residues in the ß-globin and α-globin chains, respectively. The resulting hybrid formed by these modified chains has been named Scuba hemoglobin. The in vitro production of Scuba hemoglobin by human hematopoietic stem cells and their reintroduction into the blood could be an interesting tool to improve tissue oxygenation in patients suffering from respiratory failure.