Neurotrophic strategies for treating Alzheimer's disease: lessons from basic neurobiology and animal models.

Because neurotrophic factors can prevent natural and experimental cases of neural cell death and induce and maintain differentiation, they are especially attractive agents for the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). The present report argues for the specific role of particular families of trophic factors, such as neurotrophins (e.g., nerve growth factor [NGF]) and neurokines (e.g., ciliary neurotrophic factor [CNTF]), for the promotion of the survival and phenotype of subsets of central nervous system (CNS) neurons vulnerable in AD, such as basal forebrain cholinergic neurons and cortical projection neurons. Although there is ample evidence for the therapeutic role of NGF in experimental or natural injury of cholinergic neurons, not enough progress has been made on trophic models involving cortical neurons. Further understanding of the mechanisms of cell death in AD and elucidation of the transduction cascades of trophic factors will undoubtedly refine our current concepts of a neurotrophic treatment for AD.