Methodologies

Peptide Literature

References

Product Use and Liability

Participation of gene expression in the protection against amyloid beta-peptide toxicity by the beta-amyloid precursor protein

Title

Participation of gene expression in the protection against amyloid beta-peptide toxicity by the beta-amyloid precursor protein.

Author

Barger SW; Mattson MP

Source

Ann N Y Acad Sci, 777():303-9 1996 Jan 17

Abstract

The amyloid beta-peptide (A beta) is a toxic derivative of the beta-amyloid precursor protein. Alternative processing of this precursor also yields large soluble forms (APPSs) which are secreted from many cell types. These APPSs have neuritogenic and neuroprotective activities; indeed, APPSs can protect primary neurons from the toxicity of A beta itself. To begin to explore the regulation of gene expression by APPS, we have focused on the NF-kappa B transcription factor family. NF-kappa B is induced by conditions of stress, including cellular oxidation. We report that NF-kappa B can also be induced by APPS. Furthermore, we effected direct activation of NF-kappa B through disinhibition using antisense oligonucleotide technology. This means of activating NF-kappa B resulted in protection of neuroblastoma cells from the toxicity of a calcium ionophore and protection of primary hippocampal neurons from the toxicity of A beta. Together, these data suggest that NF-kappa B may exist as a common agent inducing a neuroprotective pattern of gene expression in response to either trophic cytokines or stress itself.

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