J. Clin. Invest.
Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase.
Borrell-Pages, M., Canals, J.M., Cordelieres, F.P., Parker, J.A., Pineda, J.R., Grange, G., Bryson, E.A., Guillermier, M., Hirsch, E., Hantraye, P., Cheetham, M.E., Neri, C., Alberch, J., Brouillet, E., Saudou, F., and Humbert, S.
Notes: This study showed that the heat-shock DnaJ-containing protein 1b (HSJ1b) and cystamine are neuroprotective in Huntington disease and act by increasing release of brain-derived neurotrophic factor (BDNF), which is critical for the survival of striatal neurons. Mouse neuronal cells were transfected with vectors expressing BDNF, HSJ1b, or with a negative control (empty) vector. HSJ1b was shown to significantly increase BDNF release. Treatment of cells with cystamine, a candidate drug for treatment of Huntington disease, also increased BDNF release. RNA interference experiments showed that in cells where HSJ1b expression was reduced, cystamine no longer stimulated BDNF release, indicating that HSJ1b was required for the protective effect mediated by cystamine. In all these experiments the amount of BDNF in the cultured cell supernatants was measured using the BDNF Emax® ImmunoAssay System. (3480)
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