In high NGF concentrations, there was a shift to the right of the binding displacement curve, compared to control. Under control conditions, binding compatible with two sites corresponding to the low and high affinity receptors was observed. This was not due to a reduction in transcription. Decreased expression of TrkA on the cell surface provides the first evidence of a mechanism by which high dose NGF inhibits axonal growth. This may have important implications for the use of NGF in clinical trials for the treatment of neuropathy.
Apoptosis occurs in neurodegenerative, metabolic, and toxic diseases of the nervous system.
Death was preceded by upregulation of elements indicative of GO to G1 transition in the cell cycle. Levels of the hyperphosphorylated form of the retinoblastoma gene product increased. Use of caspase inhibitors prevented neuronal death. Inhibition of cdk activity demonstrated that the cell cycle changes were occurring upstream of caspase-3. The protective effect was abolished by K252a.