Wj. Friedman et al., SYNERGISTIC TROPHIC ACTIONS ON RAT BASAL FOREBRAIN NEURONS REVEALED BY A SYNTHETIC NGF BDNF CHIMERIC MOLECULE/, European journal of neuroscience, 7(4), 1995, pp. 656-662
Basal forebrain cholinergic neurons, which degenerate in Alzheimer's d
isease, respond to multiple trophic factors, including the neurotrophi
ns, nerve growth factor (NGF) and brain-derived neurotrophic factor (B
DNF), This dual responsiveness prompted us to investigate the effects
of a synthetic chimaeric molecule, containing the active domains of bo
th NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic a
ctions, and was 100-fold more potent than wild-type BDNF in enhancing
survival of cultured dissociated basal forebrain cholinergic neurons.
This effect was apparently due to true BDNF/NGF synergy, since additio
n of the two wildtype trophins simultaneously reproduced the effect of
the chimaera. Synergy was selective for neurons which respond to both
factors; substantia nigra dopaminergic neurons, which respond to BDNF
but not NGF, exhibited no potentiation. The chimaeric factor thus rev
ealed a synergy that may normally occur in the brain, and constitutes
a potentially novel therapeutic agent with greater potency than natura
lly occurring individual trophins.