[Apoptosis and neurotrophic factors].

Neurotrophic factors are endogenous soluble proteins regulating development, differentiation, and survival of neurons. They are secreted from target cells or surrounding glial cells and act on the neurons via their receptors on the cell membranes. Several factors are reported to promote survival of motor neurons in vitro and to rescue developing motor neurons from naturally occurring cell death. Administration of the factors has also been shown to rescue motor neurons from degeneration after axotomy in adult as well as neonatal rodents. On the basis of these lines of evidence, neurotrophic factors have been considered to be potential candidates for drugs alleviating human motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Although some factors such as ciliary neurotrophic factor and brain-derived neurotrophic factor slowed down the disease progression in animal models of motor neuron disease, phase III clinical trials showed no therapeutic effects for ALS patients treated with these factors. There may be some reasons for this lack of success in humans. Several important issues remain to be resolved such as the drug delivery systems for neurotrophic factors and combination of neurotrophic factors with complementary effects.