A non-peptidyl neurotrophic small molecule for midbrain dopaminergic neurons

Authors


Address correspondence and reprint requests to Leu-Fen H. Lin, Regeneron Pharmacueticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY, USA. E-mail: Leu-Fen.Lin@regeneron.com

Abstract

A small organic molecule (CUR-162590) that selectively enhances survival of midbrain dopaminergic neurons was identified by screening small molecule compound libraries. In embryonic midbrain cultures, CUR-162590 increased dopamine uptake and the number of dopaminergic neurons without altering the number of total neurons or astroglia or the uptake of GABA or serotonin. CUR-162590 reduced apoptosis of cultured dopaminergic neurons and protected against death induced by toxins such as MPP+. Several synthetic analogs of CUR-162590 also had similar bioactivities. CUR-162590 thus represents a new class of neurotrophic small molecules that may have utility in the treatment of Parkinson's disease, which is marked by degeneration of midbrain dopaminergic neurons.

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