Trophic protection of motor neurons: clinical potential in motor neuron diseases

Recent advances in understanding the physiologic role of nerve growth factor (NGF), obtained both from tissue culture and efficacy studies in animals, have suggested that neurotrophic factors may have clinical potential in the treatment of neurodegenerative diseases or nerve trauma [12,21]. First characterized as a target-derived survival factor for developing sympathetic and sensory neurons, it is now clear that NGF plays an important role in the maintenance and regeneration of mature peripheral neurons. Prompted by in vitro findings, it was established in the mid-1980's that intracerebroventricular infusions of NGF are capable of rescuing basal forebrain cholinergic neurons from axotomy-induced cell death produced by fimbria-fornix lesions. Given that degeneration of cholinergic neurons is a major contributing factor in the loss of cognitive function in Alzheimer's disease, there has been a great deal of interest in exploring the therapeutic potential of NGF in this disease [16]. The highly restricted specificity of NGF for sympathetic neurons, sub-populations of neural crest-derived sensory neurons and striatal and basal forebrain cholinergic neurons has for almost two decades spurred the search for other neurotrophic factors with specificities directed to the many classes of neurons which do not respond to NGF.(ABSTRACT TRUNCATED AT 250 WORDS)