Amyloid β-Peptide (10-20) (human)目录号 : GP10057
Amyloid β-Peptide (10-20) (human) 是 Amyloid-β 的片段；肽，可用于神经系统疾病的研究。
Sample solution is provided at 25 µL, 10mM.
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The amyloid β-peptide (Aβ) has a central role in initiating neurodegeneration in Alzheimer disease (AD) 1. It is widely believed to be an incidental catabolic byproduct of the amyloid β protein precursor (APP) with no normal physiological function.2
Aβ has been shown to be a ligand for a number of different receptors and other molecules3-5. It is transported between tissues and across the blood brain barrierby complex trafficking pathways6. Aβ is modulated in response to a variety of environmental stressors and is able to induce pro-inflammatory activities7.
Soluble amyloid β-peptide fragment that is a substrate for gelatinase A/type IV collagenase/MMP-2 and APP secretase; cleaved between Lys16 and Leu17.
1. Small, D.H., Mok, S.S. & Bornstein, J.C. Alzheimer’s disease and Aβ-toxicity: From top to bottom. Nature Rev. Neurosci. 2, 595–598 (2001)
2. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD (2010). Bush, Ashley I.. ed. The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide. PLoS ONE 5 (3)
3. Le Y, Gong W, Tiffany HL, Tumanov A, Nedospasov S, et al. (2001) Amyloid (b)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1.J Neurosci 21: RC123.
4. Koldamova RP, Lefterov IM, Lefterova MI, Lazo JS (2001) Apolipoprotein A-I directly interacts with amyloid precursor protein and inhibits Ab aggregation and toxicity. Biochemistry 40: 3553–3560.
5. Maezawa I, Jin LW, Woltjer RL, Maeda N, Martin GM, et al. (2004) Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment-associated cytotoxicity. J Neurochem 91: 1312–1321.
6. Tanzi RE, Moir RD, Wagner SL (2004) Clearance of Alzheimer’s Ab peptide: the many roads to perdition. Neuron 43: 605–608.
7. Paris D, Town T, Parker TA, Tan J, Humphrey J, et al. (1999) Inhibition of Alzheimer’s b-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism. Exp Neurol 157: 211–221.
|化学名||Amyloid β-Peptide (10-20) (human)|
|溶解度||≥ 144.7mg/mL in DMSO||储存条件||Desiccate at -20°C|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
|1 mg||5 mg||10 mg|
|1 mM||0.6912 mL||3.4562 mL||6.9124 mL|
|5 mM||0.1382 mL||0.6912 mL||1.3825 mL|
|10 mM||0.0691 mL||0.3456 mL||0.6912 mL|
|% DMSO % % Tween 80 % saline|
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Neuroprotective effects of donepezil against Aβ25-35-induced neurotoxicity
Purpose: The purpose of this study was to investigate the neuroprotective effect of donepezil against β-amyloid25-35 (Aβ25-35)-induced neurotoxicity and the possible mechanism. Methods: PC12 cells were conventionally cultured. Serial concentrations of Aβ25-35 and donepezil (0, 0.5, 1, 5, 10, 20 and 50 μmol/L) were added to the PC12 cells, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining was performed to detect the effects of these treatments on PC 12 viability. The PC 12 cells were pretreated with 1, 5, 10, 20 or 50 μmol/L donepezil two hours before 20 μmol/L Aβ25-35 was added to pretreatment groups A, B, C, D and E. Normal control group I and the 20 μmol/L Aβ25-35-treated group were selected. An MTT assay was used to detect PC12 cell viability, and the level of lactate dehydrogenase (LDH) was determined. PC12 cells were pretreated with 10 μmol/L GF109203X (a protein kinase C [PKC] antagonist) 30 min before 10 μmol/L donepezil was added to pretreatment group F, and normal control group II, the 10 μmol/L GF109203X-treated group and the 10 μmol/L donepezil-treated group were chosen. The expression of phosphorylation-PKC (P-PKC) and its major substrate phosphorylated myristoylated alanine-rich protein C kinase substrate (P-MARCKS) was measured by Western blotting. The effects of donepezil on the subcellular distribution of the PKCα and PKCε isoforms were detected by immunofluorescence staining. Results: Treatment with Aβ25-35 (5, 10, 20 or 50 μmol/L) for 24 h significantly (P < 0.05) decreased PC 12 cell viability in a dose-dependent manner. Compared with the PC12 cells in the control group, those in the 20 μmol/L Aβ25-35-treated group exhibited lower viability but higher LDH release. Compared with the 20 μmol/L Aβ25-35-treated group, pretreatment groups B, C, D and E exhibited significantly (P < 0.05) increased cell viability but significantly (P < 0.05) decreased LDH release. Western blotting demonstrated that compared with control, 10 μmol/L donepezil promoted PKC and MARCKS phosphorylation and that the expression of P-PKC and P-MARCKS in pretreatment group F was significantly (P < 0.05) lower than that in the donepezil-treated group. Immunofluorescence staining revealed that the PKCα and PKCε isoforms were located mainly in the cytoplasm of PC12 control cells, whereas donepezil increased the expression of the PKCα and PKCε isoforms in the membrane fraction. The Western blot results showed that donepezil altered the subcellular distribution of the PKCα and PKCε isoforms by decreasing their expression in the cytosolic fraction but increasing their expression in the membrane fraction. Conclusion: Donepezil can antagonize Aβ25-350-induced neurotoxicity in PC 12 cells, and PKC activation may account for the neuroprotective effect of donepezil.
The Use of Antimicrobial and Antiviral Drugs in Alzheimer's Disease
The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer's disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-β peptides being limited at best, a greater understanding of the physiological role of amyloid-β peptides is needed. The development of amyloid-β plaques has been determined to occur 10-20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-β peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-β plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer's disease.
Ocular biomarkers of Alzheimer's disease
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterised clinically by a progressive decline in executive functions, memory and cognition. Classic neuropathological hallmarks of AD include intracellular hyper-phosphorylated tau protein which forms neurofibrillary tangles (NFT), and extracellular deposits of amyloid β (Aβ) protein, the primary constituent of senile plaques (SP). The gradual process of pathogenic amyloid accumulation is thought to occur 10-20 years prior to symptomatic manifestation. Advance detection of these deposits therefore offers a highly promising avenue for prodromal AD diagnosis. Currently, the most sophisticated method of 'probable AD' diagnosis is via neuroimaging or cerebral spinal fluid (CSF) biomarker analysis. Whilst these methods have reported a high degree of diagnostic specificity and accuracy, they fall significantly short in terms of practicality; they are often highly invasive, expensive or unsuitable for large-scale population screening. In recent years, ocular screening has received substantial attention from the scientific community due to its potential for non-invasive and inexpensive central nervous system (CNS) imaging. In this appraisal we build upon our previous reviews detailing ocular structural and functional changes in AD (Retinal manifestations of Alzheimer's disease, Alzheimer's disease and Retinal Neurodegeneration) and consider their use as biomarkers. In addition, we present an overview of current advances in the use of fluorescent reporters to detect AD pathology through non-invasive retinal imaging.
On the biology of prions
Prions cause scrapie and Creutzfeldt-Jakob disease (CJD); these infectious pathogens are composed largely, if not entirely, of protein molecules. No prion-specific polynucleotide has been identified. Purified preparations of scrapie prions contain high titers (greater than or equal to 10(9.5) ID50/ml), one protein (PrP 27-30) and amyloid rods (10-20 nm in diameter X 100-200 nm in length). Considerable evidence indicates that PrP 27-30 is required for and inseparable from scrapie infectivity. PrP 27-30 is encoded by a cellular gene and is derived from a larger protein, denoted PrPSc or PrP 33-35Sc, by protease digestion. A cellular isoform, designated PrPC or PrP 33-35C, is encoded by the same gene as PrPSc and both proteins appear to be translated from the same 2.1 kb mRNA. Monoclonal antibodies to PrP 27-30, as well as antisera to PrP synthetic peptides, specifically react with both PrPC and PrPSc, establishing their relatedness. PrPC is digested by proteinase K, while PrPSc is converted to PrP 27-30 under the same conditions. Prion proteins are synthesized with signal peptides and are integrated into membranes. Detergent extraction of microsomal membranes isolated from scrapie-infected hamster brains solubilizes PrPC but induces PrPSc to polymerize into amyloid rods. This procedure allows separation of the two prion protein isoforms and the demonstration that PrPSc accumulates during scrapie infection, while the level of PrPC does not change. The prion amyloid rods generated by detergent extraction are identical morphologically, except for length, to extracellular collections of prion amyloid filaments which form plaques in scrapie- and CJD-infected brains. The prion amyloid plaques stain with antibodies to PrP 27-30 and PrP peptides. PrP 33-35C does not accumulate in the extracellular space. Prion rods composed of PrP 27-30 can be dissociated into phospholipid vesicles with full retention of scrapie infectivity. The murine PrP gene (Prn-p) is linked to the Prn-i gene which controls the length of the scrapie incubation period. Prolonged incubation times are a cardinal feature of scrapie and CJD. While the central role of PrPSc in scrapie pathogenesis is well established, the chemical as well as conformational differences between PrPC and PrPSc are unknown but probably arise from post-translational modifications.
Have there been improvements in Alzheimer's disease drug discovery over the past 5 years?
Alzheimer's disease (AD) is the most important neurodegenerative disorder with a global cost worldwide of over $700 billion. Pharmacological treatment accounts for 10-20% of direct costs; no new drugs have been approved during the past 15 years; and the available medications are not cost-effective. Areas covered: A massive scrutiny of AD-related PubMed publications (ps)(2013-2017) identified 42,053ps of which 8,380 (19.60%) were associated with AD treatments. The most prevalent pharmacological categories included neurotransmitter enhancers (11.38%), multi-target drugs (2.45%), anti-Amyloid agents (13.30%), anti-Tau agents (2.03%), natural products and derivatives (25.58%), novel drugs (8.13%), novel targets (5.66%), other (old) drugs (11.77%), anti-inflammatory drugs (1.20%), neuroprotective peptides (1.25%), stem cell therapy (1.85%), nanocarriers/nanotherapeutics (1.52%), and others (<1% each). Expert opinion: Unsuccessful outcomes in AD therapeutics are attributed to pathogenic misconceptions, erratic procedures in drug development and inappropriate regulations. Recommendations for the future are as follows: (i) the reconsideration of dominant pathogenic theories, (ii) the identification of reliable biomarkers, (iii) the redefinition of diagnostic criteria, (iv) new guidelines for disease management, (v) the reorientation of drug discovery programs, (vi) the updating of regulatory requirements, (vii) the introduction of pharmacogenomics in drug development and personalized treatments, and (viii) the implementation of preventive programs.