Generation of amyloid β peptide with pyroglutamate at position 3 in primary cortical neurons
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Acknowledgements
This work was supported by research grants from RIKEN Brain Science Institute, from Ministry of Education, Culture, Sports, Science and Technology, from Ministry of Health, Labour and Welfare, and Special Coordination Funds for promoting Science and Technology from Ministry of Education, Culture, Sports, Science and Technology. K.S. is a recipient of Special Postdoctoral Researchers Program. We thank Masanori Tomioka for discussion, Wakako Harigaya for technical assistance and Takeda Chemical
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2016, Journal of Biological ChemistryCitation Excerpt :Still, it remains unclear as to the cytotoxic potency of pE-Aβ peptides compared with their full-length Aβ counterparts. Some studies have demonstrated pE-Aβ peptides to have enhanced toxicity (24–26), although others have reported no difference in toxicity between the isoforms (27–30). Methodological differences may account somewhat for variability in the relative toxicities reported (Table 1), yet molecular mechanisms to explain changes in cytotoxicity have not been defined.
Interaction of dipeptydil peptidase IV with amyloid peptides
2013, Neurochemistry InternationalCitation Excerpt :But Aβ fragments starting with residue 3 were never reported when analysis of APP processing was carried out in vitro (Turner et al., 2003). It suggested that another still unknown protease may produce cleavage at position 3 in vivo, followed by cyclization of N-terminal glutamate by glutaminyl cyclase, generating pyroglutamate (Shirotani et al., 2002) and forming Aβpy(3–42). This acquires partial resistance to extracytoplasmic aminopeptidases followed by enhancing of its seeding capacity playing a critical role in the pathogenesis of AD.
N-truncated amyloid-β oligomers induce learning impairment and neuronal apoptosis
2008, Neurobiology of AgingCitation Excerpt :However, Aβ3(pE)-40 and Aβ3(pE)-42 species were not observed to be products of constitutive APP processing (Shirotani et al., 2002). Another hypothesis proposes that Aβ3(pE)-42 may be produced from the full-length (1-42) form by extracellular aminopeptidases, and then modified by glutaminyl cyclase to generate a pyroglutamylated form that might be more resistant to proteolytic degradation (Saido et al., 1995; Shirotani et al., 2002). Interestingly, the proteolysis of N-terminal cyclized parts of Aβ requires neprilysin, a metalloprotease that is reduced is AD brains (Yasojima et al., 2001).