Pharmacological up-regulation of heat shock proteins (hsps) rescues motoneurons 
from cell death in a mouse model of amyotrophic lateral sclerosis. However, the 
relationship between increased hsp expression and neuronal survival is not 
straightforward. Here we examined the effects of two pharmacological agents that 
induce the heat shock response via activation of HSF-1, on stressed primary 
motoneurons in culture. Although both arimoclomol and celastrol induced the 
expression of Hsp70, their effects on primary motoneurons in culture were 
significantly different. Whereas arimoclomol had survival-promoting effects, 
rescuing motoneurons from staurosporin and H(2)O(2) induced apoptosis, celastrol 
not only failed to protect stressed motoneurons from apoptosis under same 
experimental conditions, but was neurotoxic and induced neuronal death. 
Immunostaining of celastrol-treated cultures for hsp70 and activated caspase-3 
revealed that celastrol treatment activates both the heat shock response and the 
apoptotic cell death cascade. These results indicate that not all agents that 
activate the heat shock response will necessarily be neuroprotective.