Nerve Growth Factor (NGF) in the Central Nervous System: Implications for the Treatment of Alzheimer’s Disease
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The physiological functions of NGF in the peripheral nervous system are already known for a long time (see Levi-Montalcini and Angeletti, 1968; Greene and Shooter, 1980; Thoenen and Barde, 1980). NGF regulates the regionally differential survival of sympathetic and neural crest-derived sensory neurons. This regulatory function comes into play when the axons of NGF-responsive neurons reach their target area (see Davies et al., 1987; Barde, 1989). Furthermore, NGF is essential for the differentiation and maintenance of neuron-specific functions such as the synthesis of enzymes involved in the production of neurotransmitters and neuron-specific peptides e.g. substance P and somatostatin (see Thoenen and Barde, 1980; Otten 1984). NGF acts as a retrograde messenger transferring information from the fields of projection in the periphery to the innervating NGF-responsive neurons (see Davies et al., 1987; Barde 1989). Following Darwinian principles, NGF is produced in the target fields in very small quantities permitting the survival of a limited number of neurons only. ’Injection of exogenous NGF increases the survival of NGF responsive neurons, thus abolishing natural cell death which occurs during normal development (see Hendry, 1980; Thoenen and Barde, 1980).
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