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Participation of Gene Expression in the Protection against Amyloid β‐Peptide Toxicity by the β‐Amyloid Precursor Protein a
Author(s) -
BARGER S. W.,
MATTSON M. P.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb34437.x
Subject(s) - neuroprotection , amyloid precursor protein , toxicity , amyloid (mycology) , gene expression , chemistry , peptide , microbiology and biotechnology , nf κb , gene , biochemistry , pharmacology , biology , alzheimer's disease , signal transduction , medicine , inorganic chemistry , disease , organic chemistry
The amyloid β‐peptide (Aβ) is a toxic derivative of the β‐amyloid precursor protein. Alternative processing of this precursor also yields large soluble forms (APP S s) which are secreted from many cell types. These APP S s have neuritogenic and neuroprotective activities; indeed, APP S s can protect primary neurons from the toxicity of Aβ itself. To begin to explore the regulation of gene expression by APP S , we have focused on the NF‐κB transcription factor family. NF‐κB is induced by conditions of stress, including cellular oxidation. We report that NF‐κB can also be induced by APP S . Furthermore, we effected direct activation of NF‐κB through disinhibition using antisense oligonucleotide technology. This means of activating NF‐κB resulted in protection of neuroblastoma cells from the toxicity of a calcium ionophore and protection of primary hippocampal neurons from the toxicity of Aβ. Together, these data suggest that NF‐κB may exist as a common agent inducing a neuroprotective pattern of gene expression in response to either trophic cytokines or stress itself.