Generation of amyloid beta peptide with pyroglutamate at position 3 in primary cortical neurons.
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 precursor 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)).
Shirotani
Keiro
K
Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
Tsubuki
Satoshi
S
Lee
Hahn-Jun
HJ
Maruyama
Kei
K
Saido
Takaomi C
TC
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018076:DNA, Complementary; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*; D012845:Sindbis Virus / Q000235:genetics
D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; D011761:Pyrrolidonecarboxylic Acid