Hypothalamic gray matter changes in narcoleptic patients

globally activate the stress response (data not shown), although the Lewy body–like inclusions immunolabel for Hsp70 (ref. 5). As 3 μg/ml prevents dopaminergic cell loss due to α-synuclein toxicity, it is possible that only a modest change in or redistribution of molecular chaperones is sufficient for neuroprotection. Current anti-PD agents, including levodopa, dopamine receptor agonists (such as bromocriptine), and monoamine oxidase B inhibitors (such as deprenyl), are designed to relieve the symptoms of PD by restoring dopamine levels in the basal ganglia. Our studies define a potential drug class that promotes the survival of dopaminergic neurons. Although we suggest that geldanamycin is acting by upregulating or otherwise modulating molecular chaperone activity, the drug may also be modulating other pathways regulated by Hsp90. Regardless, these studies have revealed a drug that can fully protect against the toxicity of α-synuclein to dopaminergic neurons in Drosophila. Geldanamycin and its derivatives warrant further exploration as cytoprotective agents for the treatment of neurodegenerative diseases involving α-synuclein toxicity, including PD.