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Enhancement of β‐Amyloid Peptide Aβ(1–40)‐Mediated Neurotoxicity by Glutamine Synthetase
Author(s) -
Aksenov M. Yu.,
Aksenova M. V.,
Harris M. E.,
Hensley K.,
Butterfield D. A.,
Carney J. M.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65041899.x
Subject(s) - neurotoxicity , glutamine synthetase , senile plaques , biochemistry , beta (programming language) , amyloid beta , chemistry , cytosol , peptide , enzyme , programmed cell death , amyloid (mycology) , glutamine , biology , alzheimer's disease , toxicity , apoptosis , medicine , amino acid , disease , organic chemistry , inorganic chemistry , computer science , programming language
The β‐amyloid peptide (Aβ), a main constituent in both senile and diffuse plaques in Alzheimer's disease brains, was previously shown to be neurotoxic and to be able to interact with several macromolecular components of brain tissue. Previous investigations carried out in our laboratory demonstrated free radical species formation in aqueous solutions of Aβ(1–40) and its C‐end fragment, Aβ(25–35). Toxic forms of Aβ rapidly inactivate the oxidation‐sensitive cytosolic enzyme glutamine synthetase (GS). In this regard, we suggested and subsequently demonstrated that Aβ radicals can cause an oxidative damage of cell proteins and lipids resulting in disruption of membrane functions, enzyme inactivation, and cell death. Because GS can be a substrate for Aβ‐derived oxidizing species, the present study was conducted to determine if GS could protect against Aβ neurotoxicity. In contrast to this initial hypothesis, we here report that GS significantly enhances the neurotoxic effects of Aβ(1–40). The Aβ‐mediated inactivation of GS was found to be accompanied by the loss of immunoreactive GS and the significant increase of Aβ(1–40) neurotoxicity.