Zebrafish chemical screening reveals the impairment of dopaminergic neuronal survival by cardiac glycosides.

ABSTRACT: Parkinson's disease is a neurodegenerative disorder characterized by the prominent degeneration of dopaminergic (DA) neurons among other cell types. Here we report a first chemical screen of over 5,000 compounds in zebrafish, aimed at identifying small molecule modulators of DA neuron development or survival. We find that Neriifolin, a member of the cardiac glycoside family of compounds, impairs survival but not differentiation of both zebrafish and mammalian DA neurons. Cardiac glycosides are inhibitors of Na(+)/K(+) ATPase activity and widely used for treating heart disorders. Our data suggest that Neriifolin impairs DA neuronal survival by targeting the neuronal enriched Na(+)/K(+) ATPase α3 subunit (ATP1A3). Modulation of ionic homeostasis, knockdown of p53, or treatment with antioxida

SUBMITTER: Sun Y 

PROVIDER: S-EPMC3338518 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature