Premium
Toxicity of Pyroglutaminated Amyloid β‐Peptides 3(pE)‐40 and ‐42 Is Similar to That of Aβ1‐40 and ‐42
Author(s) -
Tekirian T. L.,
Yang A. Y.,
Glabe C.,
Geddes J. W.
Publication year - 1999
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.1471-4159.1999.0731584.x
Subject(s) - toxicity , peptide , gene isoform , chemistry , extracellular , amino acid , biochemistry , circular dichroism , in vitro , residue (chemistry) , amyloid (mycology) , stereochemistry , inorganic chemistry , organic chemistry , gene
: An N‐terminal truncated isoform of the amyloid β‐peptide (Aβ) that begins with a pyroglutamate (pE) residue at position 3 [Aβ3(pE)‐42] is the predominant isoform found in senile plaques. Based upon previous in vitro studies regarding Aβ N‐terminal truncated isoforms, it has been hypothesized that Aβ3(pE)‐x isoforms may aggregate more rapidly and become more toxic than corresponding Aβ1‐x peptides. However, the toxicity and aggregation properties of Aβ3(pE)‐42 and Aβ3(pE)‐40 have not previously been examined. After initial solubilization and 1‐week preaggregation of each peptide at 37°C and pH 7.4, the toxicity of 5‐50 μ M Aβ3(pE)‐42 was similar to that of Aβ1‐42. Moreover, the toxicity of Aβ3(pE)‐40 paralleled that induced by Aβ1‐40 in both 1 day in vitro (DIV) cortical and 7 DIV hippocampal cells. Circular dichroism spectra did not reveal major differences in secondary structure between aged Aβ1‐42, Aβ3(pE)‐42, Aβ3(pE)‐40, and Aβ1‐40 or freshly solubilized forms of these peptides. Overall, the data indicate that the loss of the two N‐terminal amino acids and the cyclization of glutamate at position 3 do not alter the extracellular toxicity of Aβ.