β-Amyloid (pE3 Peptide) Antibody

• 产品编号：CST-13172S      品牌：Cell Signaling Technology       原厂货号：13172S
• 产品分类：抗体 > 一抗 > 其它类型一抗
• 应用分类：

描述：

β-Amyloid (pE3 Peptide) Antibody 兔多抗可以识别重组的pE3形式的β-淀粉样多肽。此抗体与non-pyroglutamate (E3) 形式的β-amyloid peptides没有交叉反应。该多克隆抗体由合成的人 β-amyloid (pE3) 多肽氨基末端附近多肽免疫动物而获得。抗体由蛋白A和多肽亲和层析纯化得到。β淀粉样蛋白（A4）前体蛋白（APP）是100-140 kDa的跨膜糖蛋白，它拥有几个亚型（1）。APP的氨基酸序列中所包含的淀粉样蛋白域（A-β），能够通过两步蛋白裂解反应被释放出来（1）。释出的A-β片段在细胞外沉积积累，形成了阿尔茨海默病中淀粉样斑块的主要组成部分（1）。APP存在多个能够被磷酸化的位点，这些位点影响着蛋白本身的裂解和分泌过程（2-5）。细胞周期蛋白依赖性激酶介导的Thr688（对应于APP695亚型）磷酸化是细胞周期依赖的，在G2/M期达到峰值（4）。APP的Thr668磷酸化形式存在于成年大鼠大脑和相应的培养神经细胞及其分化细胞中（5,6）。Aβ氨基端被截短后使谷氨酸残基暴露给谷氨酰胺环化酶，谷氨酰胺环化酶能够催化氨基端焦谷氨酸(pE)d 形成(7,8)。由于Aβ (pE3)对肽酶介导的降解有耐受，因此比没有修饰过的多肽更稳定(9)，并且更倾向于形成β折叠和聚合(10)。靶向Aβ（pE3）肽的抗体是斑块特异性，因为目前还没有循环性Aβ (pE3) 肽段的证据(11)。

1. Selkoe, D.J. (1996) J Biol Chem 271, 18295-8.
2. Caporaso, G.L. et al. (1992) Proc Natl Acad Sci USA 89, 3055-9.
3. Hung, A.Y. and Selkoe, D.J. (1994) EMBO J 13, 534-42.
4. Suzuki, T. et al. (1994) EMBO J 13, 1114-22.
5. Ando, K. et al. (1999) J Neurosci 19, 4421-7.
6. Iijima, K. et al. (2000) J Neurochem 75, 1085-91.
7. Jawhar, S. et al. (2011) J Biol Chem 286, 38825-32.
8. Saido, T.C. et al. (1995) Neuron 14, 457-66.
9. Saido, T.C. et al. (1996) Neurosci Lett 215, 173-6.
10. He, W. and Barrow, C.J. (1999) Biochemistry 38, 10871-7.
11. Demattos, R.B. et al. (2012) Neuron 76, 908-20.

原厂资料：

Specificity / Sensitivity

β-Amyloid (pE3 Peptide) Antibody recognizes recombinant pE3 form of β-amyloid peptides. This antibody does not cross-react with the non-pyroglutamate (E3) form of β-amyloid peptides.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human β-amyloid (pE3) peptide. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Amyloid β (Aβ) precursor protein (APP) is a 100-140 kDa transmembrane glycoprotein that exists as several isoforms (1). The amino acid sequence of APP contains the amyloid domain, which can be released by a two-step proteolytic cleavage (1). The extracellular deposition and accumulation of the released Aβ fragments form the main components of amyloid plaques in Alzheimer's disease (1). APP can be phosphorylated at several sites, which may affect the proteolytic processing and secretion of this protein (2-5). Phosphorylation at Thr668 (a position corresponding to the APP695 isoform) by cyclin-dependent kinase is cell-cycle dependent and peaks during G2/M phase (4). APP phosphorylated at Thr668 exists in adult rat brain and correlates with cultured neuronal differentiation (5,6).

Aβ peptides can be further modified by amino-terminal truncation that exposes a free glutamate residue to the enzyme glutaminyl cyclase, which catalyzes the formation of an amino-terminal pyroglutamate (pE) (7,8). Aβ (pE3) peptides exhibit increased stability relative to non-modified peptides due to an enhanced resistance to peptidase-mediated degradation (9) and a higher propensity to form β-sheets and aggregate (10). Antibodies targeting Aβ (pE3) peptides may be plaque-specific as there is no evidence for circulating Aβ (pE3) peptides (11).

1. Selkoe, D.J. (1996) J Biol Chem 271, 18295-8.
2. Caporaso, G.L. et al. (1992) Proc Natl Acad Sci USA 89, 3055-9.
3. Hung, A.Y. and Selkoe, D.J. (1994) EMBO J 13, 534-42.
4. Suzuki, T. et al. (1994) EMBO J 13, 1114-22.
5. Ando, K. et al. (1999) J Neurosci 19, 4421-7.
6. Iijima, K. et al. (2000) J Neurochem 75, 1085-91.
7. Jawhar, S. et al. (2011) J Biol Chem 286, 38825-32.
8. Saido, T.C. et al. (1995) Neuron 14, 457-66.
9. Saido, T.C. et al. (1996) Neurosci Lett 215, 173-6.
10. He, W. and Barrow, C.J. (1999) Biochemistry 38, 10871-7.
11. Demattos, R.B. et al. (2012) Neuron 76, 908-20.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody.