Prolonged denervation results in atrophy of target organs and increased risk of permanent paralysis. A better understanding of the mechanism responsible for nerve regeneration may one day lead to improved rates of nerve regeneration and diminished risk of loss of function. Neurobiologists have known for decades that soluble neurotrophic activity is present in nerves and nerve targets. Until recently, the soluble molecules that regulate the rate of nerve regeneration have eluded identification. Insulin-like growth factor (IGF) gene expression is correlated with synapse formation during development and regeneration. IGFs are now identified as the first soluble nerve- and muscle-derived neurotrophic factors found to regulate the rate of peripheral nerve regeneration. The roles of IGFs and other neurotrophic factors in peripheral nerve regeneration, motor nerve terminal sprouting and synapse formation are reviewed.
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