Generation of amyloid β peptide with pyroglutamate at position 3 in primary cortical neurons

被引:24
作者
Shirotani, K
Tsubuki, S
Lee, HJ
Maruyama, K
Saido, TC
机构
[1] RIKEN, Brain Sci Inst, Lab Proteolyt Neurosci, Wako, Saitama 3510198, Japan
[2] Saitama Med Sch, Dept Pharmacol, Moroyama, Saitama 3500495, Japan
关键词
Alzheimer's disease; amyloid beta peptide; pyroglutamate; primary neuron; Sindbis virus; mass spectrometry;
D O I
10.1016/S0304-3940(02)00351-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The majority of amyloid beta peptide (Abeta) deposited in the brains of Alzheimer's disease (AD) patients is N-truncated, especially Abeta starting with pyroglutamate at position 3 (Abeta(3(pE))). To develop a system in which Abeta(3(pE)) is generated in primary neurons and to clarify the cyclization mechanism of N-terminal glutamate, we constructed amyloid precurosr protein complementary DNAs which encoded a potential precursor for Abeta(3(pE)) by amino acid substitution and deletion. Among them, expression of NLQ construct by Sindbis virus resulted in secretion of Abeta(3(pE)) from primary neurons, whereas the N-termini of Abeta derived from NL and NLE constructs were intact. Therefore, the NLQ construct would be useful in establishing an animal model which produces Abeta(3(pE)). (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:25 / 28
页数:4
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