Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain

Topic: Brain proteins, microglia and lab models

Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the beta protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the beta-protein precursor (beta-PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and beta-PP mRNAs. The increases in PrP and beta-PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and beta-PP mRNA levels. Increased PrP and beta-PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and beta-PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

@article{mobley1988-2904679,
  author  = {Mobley, W. C. and Neve, R. L. and Prusiner, S. B. and McKinley, M. P.},
  title   = {{Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1988},
  doi     = {10.1073/pnas.85.24.9811},
  pmid    = {2904679},
  url     = {https://doi.org/10.1073/pnas.85.24.9811}
}

Key findings

• We found that gene expression for PrP and the beta-protein precursor (beta-PP) is regulated in developing hamster brain.

Why it matters

In developing hamster brain, injections of nerve growth factor increased mRNA levels for the prion protein and the beta-amyloid protein precursor in regions containing NGF-responsive cholinergic neurons. This is animal work on gene regulation and does not show any way to treat, cure or prevent Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.85.24.9811
• PubMed: 2904679
• Original source →
• Free full text: PubMed Central →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature · 1987-02-01 · usefulness score 58/100 · Disease mechanisms
• Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science (New York, N.Y.) · 1987-02-01 · usefulness score 57/100 · Down syndrome and Alzheimer's
• Amyloid plaque core protein in Alzheimer disease and Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1985-06-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochemical and Biophysical Research Communications · 1984-05-01 · usefulness score 54/100 · Disease mechanisms

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