Nerve growth factor signaling, neuroprotection, and neural repair

Nerve growth factor (NGF) was discovered 50 years ago as a molecule that pr omoted the survival and differentiation of sensory and sympathetic neurons. Its roles in neural development have been characterized extensively, but r ecent findings point to an unexpected diversity of NGF actions and indicate that developmental effects are only one aspect of the biology of NGF. This article considers expanded roles for NGF that are associated with the dyna mically regulated production of NGF and its receptors that begins in develo pment, extends throughout adult life and aging, and involves a surprising v ariety of neurons, glia, and nonneural cells. Particular attention is given to a growing body of evidence that suggests that among other roles, endoge nous NGF signaling subserves neuroprotective and repair functions. The anal ysis points to many interesting unanswered questions and to the potential f or continuing research on NGF to substantially enhance our understanding of the mechanisms and treatment of neurological disorders.