Target: Amyloid Beta Pyroglutamate 3-42
Nature: Synthetic (TFA preparation, HFIP treated precursor)
Swiss-Prot: P05067
Biological Activity:
Expression System: N/A
Protein Length: 40 amino acids
Amino Acid Sequence: pyroEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA
Purification: N/A
Purity: >95%
Storage Buffer: 10mM HCl with 2% DMSO
Protein Size: 4.3 kDa
Conjugate: No Tag
Cellular Localization: Cell Membrane,Intracellular Vesicles
Scientific Background: Our Amyloid Beta pyroglutamate 3-42 (pyro Aβ) Pre-formed Fibrils are generated from Amyloid Beta Peptide 3-42 pre-treated with 1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) using a previously published method (1,2). Our pyro Aβ3-42 fibrils present as primarily long strands when observed under TEM and AFM, and have a unique high molecular weight signal on a Western Blot with an anti-amyloid beta antibody.Amyloid beta peptide (Aβ) is generated by protease cleavage of amyloid precursor protein (APP), which aggregates into oligomers, protofibrils, fibrils and ultimately plaques. The accumulation of Aβ plaques in the brain is considered a hallmark of Alzheimer’s disease (AD), and most of the drugs tested for AD in the past 20 years have targeted amyloid beta accumulation (3). Pyroglutamate Aβ 3-42 is an N-terminally truncated peptide species that is modified by glutaminyl cyclase and has been reported to compromise 15-45% of total amyloid beta deposits in brains of AD patients (4,5). Pyroglutamate Aβ 3-42 exhibits higher aggregation propensity and neurotoxicity compared with full-length Aβ 1-42 (6,7) and is an active target in the next generation AD therapeutic development (8).
References: 1. Stine et al. 2003. JBC. 278(13):11612-22; doi: 10.1074/jbc.M2102072002. Chromy et al. 2003. Biochemistry. 42:12749-12760; doi: 10.1021/bi030029q3. Panza et al. 2019. Nat Rev Neurol. 15:73-88; https://doi.org/10.1038/s41582-018-0116-64. Valverde et al. 2021. JBC. 297:100963; https://doi.org/10.1016/j.jbc.2021.1009635.Schilling et al. 2008. Nat Med. 14:1106-11; DOI: 10.1038/nm.18726.Hartlage-Rubsamen et al. 2011. Acta Neuropathol. 121:705-19; 10.1007/s00401-011-0806-27.Xu, Wang and Wu. 2021. J Med Chem. 64:6549–65; DOI: 10.1021/acs.jmedchem.1c003258.Bayer. 2021. Nat Mol Psych. 27:1880-1885; https://doi.org/10.1038/s41380-021-01409-3
Field of Use: Not for use in humans. Not for use in diagnostics or therapeutics. For research use only.
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