Toxicity of Pyroglutaminated Amyloid β-Peptides 3(pE)-40 and -42 Is Similar to That of Aβ1-40 and -42.

Autor: Tekirian, T. L., Yang, A. Y., Glabe, C., Geddes, J. W.
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Zdroj: Journal of Neurochemistry; Oct99, Vol. 73 Issue 4, p1584-1589, 6p
Abstrakt: Abstract: 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 μM 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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