β-Amyloid (1-42), human TFA
(Synonyms: 大豆肽) 目录号 : GC16243
淀粉样蛋白 β 肽 (1-42) 人 TFA 是一种由 42 个氨基酸组成的肽。
Cas No.:107761-42-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
| Cell experiment [1]: | |
|
Cell lines |
PC12, cerebral cortex neurons |
|
Preparation Method |
β-Amyloid (1-42), human TFA was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 1 mM and pre-incubated at 37°C for 7 days to promote aggregation and then diluted in medium, then oligomerized β-Amyloid (1-42) (equivalent to 1 mM peptides) were prepared for β-Amyloid (1-42) insult experiments. For PC12 cellular AD model construction, PC12 cells were firstly cultured in 20 ng/ml nerve growth factor (NGF) and 10% FBS for 72 h at 37°C with 95% air and 5% CO2 to promote PC12 cells differentiation, and then 1 uM of oligomerized β-Amyloid (1-42) were added for 24 h to build PC12 cellular AD models. For cellular AD model of cerebral cortex neurons, 1 mM of oligomerized β-Amyloid (1-42) peptides was added in primary cerebral cortex neurons for 24 h to build cellular AD model of cerebral cortex neurons. |
|
Reaction Conditions |
1 uM for 24 h |
|
Applications |
Cell viability was reduced in β-Amyloid (1-42) insult group compared with a control group in NGF stimulated PC 12 cells and primary cerebral cortex neurons from rat embryo cells, indicating successes in the construction of cellular AD models. |
| Animal experiment [2]: | |
|
Animal models |
Male Wistar rats weighing 210-230 g |
|
Preparation Method |
AD model was induced by β-Amyloid (1-42) dissolved in normal saline at the concentration of 4 µg/µl. The solution was kept at room temperature for 3 days before administration75. β-Amyloid (1-42) or saline was injected in a volume of 2 µl over 5 min via a microsyringe pump connected to the 25-gauge stainless steel needle bilaterally into the lateral cerebral ventricles according to stereotaxic coordination. |
|
Dosage form |
4 µg/µl, 2 µl, lateral cerebral ventricle injection |
|
Applications |
Immunostaining of β-Amyloid (1-42) of entorhinal cortex (EC), and dorsal hippocampus (dHPC) sections demonstrated a high level of Aβ plaques in β-Amyloid (1-42) animals compared to the saline group. |
|
References: [1]: Yang H, Wang H, Shang H, et al. Circular RNA circ_0000950 promotes neuron apoptosis, suppresses neurite outgrowth and elevates inflammatory cytokines levels via directly sponging miR-103 in Alzheimer's disease[J]. Cell Cycle, 2019, 18(18): 2197-2214. |
|
Amyloid β-Peptide (1-42) human TFA is a 42-amino acid peptide. Alzheimer's disease (AD) is characterized phenotypically by memory impairment, neurochemically by accumulation of β-amyloid peptide (such as β-Amyloid (1-42)) and morphologically by an initial loss of nerve terminals in cortical and hippocampal regions [1]. the abnormal production of soluble forms of β-amyloid peptides (Aβ), such as β-Amyloid (1-42), have been proposed as a major culprit in AD [2].
β-Amyloid (1-42) can impair synaptic function, typified by its ability to affect synaptic plasticity [3], and trigger events leading to a loss of viability of synapses [4], and leads to memory impairment [5]. The intracerebroventricular administration of β-Amyloid (1-42) has been proposed as a model of AD [6].
β-Amyloid (1-42) (100 μg/ml) for 24 h cell viability ofSH-SY5Y cells dropped to about 50%, β-Amyloid (1-42)-induced cell apoptosis could be completely prevented by EGb761 at 100 μg/ml and to a lesser extent, by quercetin (1.5 μg/ml) and ginkgolide B (10 μg/ml) [7].
β-Amyloid (1-42) (icv. 2 nmol in 4 μl) caused a predominant loss of glutamatergic and cholinergic markers [1].β-Amyloid (1-42) was combined with inducers of oxidative stress to induce neuronal cell death, amyloid deposits, gliosis and memory impairment following a 4 week intracerebroventricular infusion. Oxidative stress was induced using the pro-oxidative cation Fe2+ and the glutathione synthesis inhibitor buthionine sulfoximine (BSO) [8].
References:
[1].Canas P M, Sim?es A P, Rodrigues R J, et al. Predominant loss of glutamatergic terminal markers in a β-amyloid peptide model of Alzheimer's disease[J]. Neuropharmacology, 2014, 76: 51-56.
[2].Hardy J, Selkoe D J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics[J]. science, 2002, 297(5580): 353-356.
[3].Venkitaramani D V, Chin J, Netzer W J, et al. β-amyloid modulation of synaptic transmission and plasticity[J]. Journal of Neuroscience, 2007, 27(44): 11832-11837.
[4].Mattson M P, Partin J, Begley J G. Amyloid β-peptide induces apoptosis-related events in synapses and dendrites[J]. Brain research, 1998, 807(1-2): 167-176.
[5].Selkoe D J. Soluble oligomers of the amyloid β-protein: Impair synaptic plasticity and behavior[J]. Synaptic Plasticity and the Mechanism of Alzheimer's Disease, 2008: 89-102.
[6].Lawlor P A, Young D. Aβ infusion and related models of Alzheimer dementia[M]//Animal models of Dementia. Humana Press, 2011: 347-370.
[7].Shi C, Zhao L, Zhu B, et al. Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against β-amyloid peptide-induced toxicity in SH-SY5Y cells[J]. Chemico-biological interactions, 2009, 181(1): 115-123.
[8].Lecanu, L., Greeson, J., & Papadopoulos, V. (2006). Beta-amyloid and oxidative stress jointly induce neuronal death, amyloid deposits, gliosis, and memory impairment in the rat brain. Pharmacology, 76(1), 19-33.
淀粉样蛋白 β 肽 (1-42) 人 TFA 是一种由 42 个氨基酸组成的肽。阿尔茨海默氏病 (AD) 的表型特征是记忆障碍,神经化学特征是 β-淀粉样肽（例如 β-淀粉样蛋白 (1-42)）的积累,形态特征是皮层和海马区域神经末梢的初始丧失 [ 1]。 β-淀粉样蛋白 (1-42) 等可溶性形式的 β-淀粉样肽 (Aβ) 的异常生成被认为是 AD [2] 的罪魁祸首。
β-淀粉样蛋白 (1-42) 可损害突触功能,其典型特征是其影响突触可塑性的能力[3],并触发导致突触活力丧失的事件[ 4],并导致记忆障碍[5]。脑室内注射β-淀粉样蛋白（1-42）已被提议作为AD的模型[6]。
β-淀粉样蛋白 (1-42) (100 μg/ml) 24 小时后,SH-SY5Y 细胞的细胞活力下降至约 50%,β-淀粉样蛋白 (1-42) 诱导的细胞凋亡可被 EGb761 完全阻止100 μg/ml 和较小程度的槲皮素 (1.5 μg/ml) 和银杏内酯 B (10 μg/ml) [7]。
β-淀粉样蛋白 (1-42)（icv. 2 nmol in 4 μl）导致谷氨酸能和胆碱能标记物的主要损失[1]。β-淀粉样蛋白 (1-42) 结合在 4 周的脑室内输注后,用氧化应激诱导剂诱导神经元细胞死亡、淀粉样蛋白沉积、神经胶质增生和记忆障碍。使用促氧化阳离子 Fe2+ 和谷胱甘肽合成抑制剂丁硫氨酸亚砜亚胺 (BSO) [8] 诱导氧化应激。
| Cas No. | 107761-42-2 | SDF | |
| 别名 | 大豆肽 | ||
| 分子式 | C203H311N55O60S | 分子量 | 4514.08 |
| 溶解度 | Soluble to 1 mg/ml in 50mM Tris buffer | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 0.2215 mL | 1.1076 mL | 2.2153 mL |
| 5 mM | 0.0443 mL | 0.2215 mL | 0.4431 mL |
| 10 mM | 0.0222 mL | 0.1108 mL | 0.2215 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Fibril structure of amyloid-β(1-42) by cryo-electron microscopy
Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth.
α-synuclein-assisted oligomerization of β-amyloid (1-42)
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders, characterized by aggregation of amyloid polypeptides, β-amyloid (Aβ) and α-synuclein (αS), respectively. Aβ and αS follow similar aggregation pathways, starting from monomers, to soluble toxic oligomeric assemblies, and to insoluble fibrils. Various studies have suggested overlaps in the pathologies of AD and PD, and have shown Aβ-αS interactions. Unfortunately, whether these protein-protein interactions lead to self- and co-assembly of Aβ and αS into oligomers - a potentially toxic synergistic mechanism - is poorly understood. Among the various Aβ isoforms, interactions of Aβ containing 42 amino acids (Aβ (1-42), referred to as Aβ42) with αS are of most direct relevance due to the high aggregation propensity and the strong toxic effect of this Aβ isoform. In this study, we carefully determined molecular consequences of interactions between Aβ42 and αS in their respective monomeric, oligomeric, and fibrillar forms using a comprehensive set of experimental tools. We show that the three αS conformers, namely, monomers, oligomers and fibrils interfered with fibrillization of Aβ42. Specifically, αS monomers and oligomers promoted oligomerization and stabilization of soluble Aβ42, possibly via direct binding or co-assembly, while αS fibrils hindered soluble Aβ42 species from converting into insoluble aggregates by the formation of large oligomers. We also provide evidence that the interactions with αS were mediated by various parts of Aβ42, depending on Aβ42 and αS conformers. Furthermore, we compared similarities and dissimilarities between Aβ42-αS and Aβ40-αS interactions. Overall, the present study provides a comprehensive depiction of the molecular interplay between Aβ42 and αS, providing insight into its synergistic toxic mechanism.
Aβ1-42 peptide toxicity on neuronal cells: A lipidomic study
Currently Alzheimer's Disease (AD) pathological pathways, which lead to cell death and dementia, are not completely well-defined; in particular, the lipid changes in brain tissues that begin years before AD symptoms. Due to the central role of the amyloid aggregation process in the early phase of AD pathogenesis, we aimed at developing a lipidomic approach to evaluate the amyloid toxic effects on differentiated human neuroblastoma derived SH-SY5Y cells. First of all, this work was performed to highlight qualitative and relative quantitative lipid variations in connection with amyloid toxicity. Then, with an open outcome, the study was focused to find out some new lipid-based biomarkers that could result from the interaction of amyloid peptide with cell membrane and could justify neuroblastoma cells neurotoxicity. Hence, cells were treated with increasing concentration of Aβ1-42 at different times, then the lipid extraction was carried out by protein precipitation protocol with 2-propanol-water (90:10 v/v). The LC-MS analysis of samples was performed by a RP-UHPLC system coupled with a quadrupole-time-of-flight mass spectrometer in comprehensive data - independent SWATH acquisition mode. Data processing was achieved by MS-DIAL. Each lipid class profile in SH-SY5Y cells treated with Aβ1-42 was compared to the one obtained for the untreated cells to identify (and relatively quantify) some altered species in various lipid classes. This approach was found suitable to underline some peculiar lipid alterations that might be correlated to different Aβ1-42 aggregation species and to explore the cellular response mechanisms to the toxic stimuli. The in vitro model presented has provided results that coincide with the ones in literature obtained by lipidomic analysis on cerebrospinal fluid and plasma of AD patients. Therefore, after being validated, this method could represent a way for the preliminary identification of potential biomarkers that could be researched in biological samples of AD patients.
New Aβ(1-42) ligands from anti-amyloid antibodies: Design, synthesis, and structural interaction
Alzheimer's disease (AD), is the most common neurodegenerative disorder of the aging population resulting in progressive cognitive and functional decline. Accumulation of amyloid plaques around neuronal cells is considered a critical pathogenetic event and, in most cases, a hallmark of the pathology. In the attempt to identify anti-AD drug candidates, hundreds of molecules targeting Aβ peptides have been screened. Peptide molecules have been widely explored, appreciating chemical stability, biocompatibility, and low production cost. More recently, many anti-Aβ(1-42) monoclonal antibodies have been developed, given the excellent potential of immunotherapy for treating or preventing AD. Antibodies are versatile ligands that bind a large variety of molecules with high affinity and specificity; however, their extensive therapeutic application is complex and requires huge economic investments. Novel approaches to identify alternative antibody formats are considered with great interest. In this context, taking advantage of the favorable peptide properties and the availability of Aβ-antibodies structural data, we followed an innovative research approach to identify short peptide sequences on the model of the binding sites of Aβ(1-42)/antibodies. WAibH and SYSTPGK were designed as mimics of solanezumab and aducanumab, respectively. Circular dichroism and nuclear magnetic resonance analysis reveal that the antibody-derived peptides interact with Aβ(1-42) in the soluble monomeric form. Moreover, AFM microscopy imaging shows that WAibH and SYSTPGK are capable of controlling the Aβ(1-42) aggregation. The strategy to identify WAibH and SYSTPGK is innovative and can be widely applied for new anti-Aβ antibody mimicking peptides.
Matriptase cleaves the amyloid-beta peptide 1-42 at Arg-5, Lys-16, and Lys-28
Objective: The type-II transmembrane extracellular serine protease matriptase was shown to cleave at Arg-102 in the amino-terminal region of the amyloid precursor protein (APP). In this study we determined matriptase cleavage sites in the amyloid-beta (Aβ) peptide region of APP (Asp-597 to Ala-638 in the APP695 isoform). A recombinant human matriptase protease domain was used to cleave a synthetic human Aβ1-42 peptide. The human APP695 or mutants at the candidate matriptase cleavage sites was co-expressed with the human matriptase or its protease-dead mutant in HEK293 cells to evaluate matriptase cleavage of APP. Overexpression of matriptase in the M17 human neuroblastoma cells was performed to determine the effect of matriptase expression on endogenous APP.
Results: The human Aβ1-42 peptide can be cleaved by the matriptase serine protease domain, at Arg-5, Lys-16, and Lys-28, as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Co-expression of matriptase but not its protease-dead mutant with APP695 resulted in site-specific cleavages of the latter. Replacement of Arg-601 (Arg-5 in Aβ1-42) by Ala in APP695 prevented matriptase cleavage at this site. Overexpression of matriptase but not its protease-dead mutant in the M17 cells resulted in a significant reduction of the endogenous APP quantity.