Malonate-induced cortico-motoneuron death is attenuated by NT-4, but not by BDNF or NT-3

Neurotrophins are promising candidates to slow the progression of amyotroph ic lateral sclerosis (ALS), a neurodegenerative disease in which spinal and cortical motoneurons selectively degenerate. In a long-term in vitro model , malonate-induced toxicity and cell death of motoneurons have been demonst rated. Here we studied the neuroprotective effect of BDNF, NT-3, and NT-4 o n the cell death of cortical motoneurons in an organotypic culture model af ter chronic mitochondrial inhibition with malonate. Our data show that NT-4 completely prevents: malonate-induced toxicity, whereas BDNF or NT-3 had n o neuroprotective effect. In clinical trials for ALS, predominantly focusse d on the survival of spinal motoneurons, BDNF has already been tested with disappointing results; our results suggest that NT-4 may be a better neurot rophin to prevent motoneuron loss. NeuroReport 12:1355-1358. (C) 2001 Lippi ncott Williams & Wilkins.