Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients....

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Detalles Bibliográficos
Autores: Borrell Pagès, Maria, Canals i Coll, Josep M., Cordelières, Fabrice P., Parker, J. Alex, Pineda Martí, José Ramón, Grange, Ghislaine, Bryson, Elzbieta A., Guillermier, Martine, Hirsch, Etienne, Hantraye, Philippe, Cheetham, Michael E., Néri, Christian, Alberch i Vié, Jordi, 1959-, Brouillet, Emmanuel, Saudou, Frédéric, Humbert, Sandrine
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2006
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/8314
Acceso en línea:https://hdl.handle.net/2445/8314
Access Level:acceso abierto
Palabra clave:Corea de Huntington
Degeneració del sistema nerviós
Quimioteràpia
Huntington's chorea
Neurodegenerative Diseases
Chemotherapy
Descripción
Sumario:There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin¿induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.

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