Involvement of Protein Kinase C in the Regulation of Nerve Growth Factor Synthesis: A Possible Cause of Impaired Trophic Supply in Alzheimer’s Disease?

  • P. Brachet
  • R. Houlgatte
  • I. Neveu
  • D. MacGrogan
  • D. Wion
Conference paper
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Summary

It is of interest to characterize the regulatory mechanisms which control the synthesis of nerve growth factor (NGF) in order to design pharmacological procedures that might modulate the production of neurotrophic factor in vivo. This approach may be of valuable help in minimizing the deleterious effects of neurodegenerative diseases such as Alzheimer’s disease, which may affect NGF-responsive neurons.

Experiments performed with a line of mouse fibroblast-like cells demonstrated that serum increases the level of expression of NGF gene. The effect of serum on the NGF mRNA pool may be prevented by inhibitors of protein kinase activities, such as compound K 252a. This suggests that a protein phosphorylation step is involved in the up-regulation of NGF synthesis. The effect of serum can be mimicked both in fibroblasts and primary cultures of glial cells by the protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). This mechanism may be altered in neuropathological disorders such as Alzheimer’s disease or diabetes-associated peripheral neuropathy, where impaired or decreased protein kinase C activity is thought to take place.

Keywords

Nerve Growth Factor Basal Forebrain Nerve Growth Factor mRNA Choline Acetyl Transferase Nerve Growth Factor Protein 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • P. Brachet
  • R. Houlgatte
  • I. Neveu
  • D. MacGrogan
  • D. Wion

There are no affiliations available

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