Active Recombinant Human APP/Protease Nexin II, CF

• Cat.No.: APP-54H
• Product Overview: A DNA sequence encoding the human CD33 signal peptide and the ectodomain of the recombinant human A Disintegrin and Metalloprotease domain 10 (rhADAM10, amino residues 18 - 672) (Rosendahl, et al., 1997, J. Biol. Chem. 272:24588 - 24593) was expressed with a C-terminal 10X His tag in an insect cell line, Sf21.

Specification

• Description: ADAM10 (also known as Kuzbanian, mammalian disintegrin metalloprotease, myelin-associated metalloproteinase) is a member of the ADAM family that contains a disintegrin and metalloprotease-like domain. Like other membrane-anchored ADAMs, ADAM10 consists of the following domains, pro with a cysteine switch and furin cleavage sequence, catalytic with the zinc-binding site and Met-turn expected for reprolysins, disintegrin-like, cystein-rich, EGF-like, transmembrane, and cytoplasmic. ADAM10 is highly conserved, with 97% amino acid identity between mouse, rat, cattle and human and 45% identity between mouse and the active enzyme processes notch, notch ligand delta, and amyloid protein precursor at the alpha site, playing an important role in neurogenesis.
• Source: Insect Sf21 cell line
• Species: Human
• Tag: His
• Bio-activity: Measured by its ability to cleave a fluorescent peptide substrate, (7-methoxycoumarin-4-yl) acetyl-Pro-Leu-Ala-Gln-Ala-Val-(3-[2, 4-dinitrophenyl]-L-2, 3-diaminopropionyl)-Arg-Ser-Ser-Ser-Arg -NH2 . Cleavage of ES003 can be measured using excitation and emission wavelengths of 320 nm and 405 nm, respectively.
• Molecular Mass: The purified secreted rmADAM10 exists as the mature and active form with the N-terminal sequence of T214TSAEKNTCQ. The 469 amino acid residue rhADAM10 has a predicted molecular mass of approximately 52 kDa. By SDS-PAGE, the apparent molecular mass is appr
• Endotoxin: < 2.0 eu per 1 μg of the enzyme as determined by the lal
• Purity: >90%, as determined by SDS-PAGE and visualized by silver stain
• Storage: Lyophilized samples are stable for up to six months at -20° C to -70° C. Upon reconstitution, this cytokine, in the presence of a carrier protein, can be stored under sterile conditions at 2 - 8° C for one month or at -20° C to -70° C in a manual defrost freezer for three months without detectable loss of activity.

Gene Information

• Gene Name: APP amyloid beta (A4) precursor protein [ Homo sapiens ]
• Official Symbol: APP
• Synonyms: APP; amyloid beta (A4) precursor protein; AD1, Alzheimer disease; amyloid beta A4 protein; peptidase nexin II; preA4; protease nexin-II; peptidase nexin-II; beta-amyloid peptide; alzheimer disease amyloid protein; cerebral vascular amyloid peptide; AAA; AD1; PN2; ABPP; APPI; CVAP; ABETA; PN-II; CTFgamma
• Gene ID: 351
• mRNA Refseq: NM_000484
• Protein Refseq: NP_000475
• MIM: 104760
• UniProt ID: P05067
• Chromosome Location: 21q21.2
• Pathway: Activated TLR4 signalling, organism-specific biosystem; Advanced glycosylation endproduct receptor signaling, organism-specific biosystem; Alzheimers disease, organism-specific biosystem; Alzheimers disease, conserved biosystem; Amyloids, organism-specific biosystem; Caspase cascade in apoptosis, organism-specific biosystem; Class A/1 (Rhodopsin-like receptors), organism-specific biosystem
• Function: DNA binding; PTB domain binding; acetylcholine receptor binding; heparin binding; identical protein binding; peptidase activator activity; peptidase inhibitor activity; protein binding; receptor binding; serine-type endopeptidase inhibitor activity; transition metal ion binding

Reviews

11/19/2021

This can be advantageous in understanding disease mechanisms and developing novel therapeutics.

07/28/2019

APP protein is highly recommended for various research applications, including ELISA and protein electron microscopy structure analysis.

12/23/2017

The manufacturer can provide detailed documentation on the quality control measures undertaken during protein production and purification.

04/29/2016

APP protein might have biomarker properties, meaning its levels or activity could be indicative of disease progression or treatment response.

Q&As

Are there any ongoing research efforts targeting the APP protein for Alzheimer's disease treatment?

Yes, there is ongoing research focused on developing therapies that target the APP protein and its associated pathways in Alzheimer's disease. These include clinical trials investigating the effectiveness of anti-amyloid antibodies, small molecule inhibitors of amyloid-beta production, and modulators of APP processing enzymes. Additionally, other approaches targeting downstream processes related to APP or amyloid-beta toxicity are also being explored.

How does the APP protein contribute to synaptic dysfunction in Alzheimer's disease?

The excessive accumulation of amyloid-beta peptides in Alzheimer's disease leads to synaptic dysfunction and loss. Amyloid-beta can disrupt neurotransmitter signaling, impair synaptic plasticity, and induce inflammation, ultimately leading to cognitive impairment and memory deficits commonly observed in Alzheimer's disease.

Are there any potential therapeutic strategies targeting APP protein dysregulation?

Yes, there are various therapeutic strategies being explored to target APP protein dysregulation in Alzheimer's disease. One approach is to reduce the production or aggregation of amyloid-beta, which is derived from APP cleavage. This can be done through the use of small molecule inhibitors or antibodies that target the enzymes involved in APP cleavage or amyloid-beta aggregation. Another approach is to modulate the expression or processing of APP itself, aiming to reduce the production of amyloid-beta.

How is the APP protein processed and cleaved in the brain?

The APP protein can undergo two main pathways of processing. The non-amyloidogenic pathway involves the cleavage of APP by alpha-secretase, producing soluble APP-alpha (sAPPα) and preventing the formation of amyloid-beta. The amyloidogenic pathway involves sequential cleavage by beta-secretase and gamma-secretase, resulting in the generation of amyloid-beta peptides of various lengths.

Are there any therapeutic strategies targeting the APP protein in Alzheimer's disease?

Numerous therapeutic strategies have been explored to target the APP protein and the production of amyloid-beta in Alzheimer's disease. These include inhibiting the enzymes responsible for amyloid-beta formation (beta-secretase and gamma-secretase), immunotherapies targeting amyloid-beta, and modulating APP processing and trafficking.

Are there any non-genetic factors that can influence APP protein dysregulation?

Yes, certain lifestyle and environmental factors have been associated with increased APP protein dysregulation. For example, chronic oxidative stress, inflammation, and metabolic dysfunction can impact APP processing and amyloid-beta production. Additionally, lifestyle choices such as a sedentary lifestyle, poor diet, and chronic stress may also contribute to APP dysregulation and the risk of developing Alzheimer's disease.

Can imaging techniques detect amyloid-beta plaques in the brain?

Yes, there are several imaging techniques, such as positron emission tomography (PET) using specific radioactive tracers, that can detect and quantify amyloid-beta plaque deposition in the brain. These imaging modalities are clinically used to support the diagnosis of Alzheimer's disease and monitor disease progression.

Can the APP protein be targeted for diagnostic purposes?

While the measurement of APP protein levels or its cleavage products in biological samples has shown promise as a diagnostic tool for Alzheimer's disease, it is not currently used in routine clinical practice. The sensitivity and specificity of these measurements need to be further improved to ensure their accuracy and reliability for diagnostic purposes.

Is the APP protein involved in any other diseases or conditions?

Besides its role in Alzheimer's disease, the APP protein has been implicated in other neurodegenerative disorders such as Down syndrome and cerebral amyloid angiopathy. Additionally, it may play a role in certain types of cancers, as altered APP expression has been observed in some tumors.

Are there any known risk factors associated with APP protein dysregulation?

While genetic mutations in the APP gene are associated with familial Alzheimer's disease, there are also other risk factors that can influence APP protein dysregulation. Age is the most significant risk factor, as the incidence of Alzheimer's disease increases with age. Other factors such as genetic variations in other genes, lifestyle choices (e.g., smoking, diet, exercise), and environmental factors may also contribute to APP protein dysregulation and the development of the disease.

Can changes in APP protein expression or processing be detected in animal models of Alzheimer's disease?

Yes, animal models of Alzheimer's disease play an important role in studying changes in APP protein expression and processing. These models mimic certain aspects of Alzheimer's disease pathology, enabling researchers to investigate the effects of genetic and environmental manipulations on APP metabolism and amyloid-beta production. They help in understanding disease mechanisms and testing potential therapeutic interventions.

Can the APP protein be measured in biological samples for diagnostic purposes?

Yes, the measurement of APP protein or its cleavage products can be performed in cerebrospinal fluid (CSF) and blood samples. These measurements are explored for their potential diagnostic value and monitoring disease progression in Alzheimer's disease. However, they are not currently used as routine diagnostic tools due to limitations in sensitivity and specificity.

What are the potential functions of amyloid-beta produced from APP cleavage?

The functional role of amyloid-beta peptides is not entirely clear. Some studies suggest that amyloid-beta may have antimicrobial properties, play a role in synaptic activity, or act as a neuroprotectant. However, it is thought that abnormal accumulation of amyloid-beta contributes to neurotoxicity and neurodegeneration in Alzheimer's disease.

Does the APP protein have any known physiological roles outside the brain?

Yes, the APP protein is not limited to the brain and has been found in various tissues and cell types throughout the body. While its function outside the brain is less understood, studies suggest its involvement in processes such as cell adhesion, wound healing, fertilization, and tissue repair. However, further research is needed to fully elucidate its physiological roles beyond the brain.

Are there any known compounds or drugs that can modulate APP protein expression or processing?

Several compounds and drugs have shown potential in modulating APP protein expression or processing in preclinical and clinical studies. Examples include gamma-secretase inhibitors, beta-secretase inhibitors, and anti-amyloid antibodies. However, the development of effective and safe therapeutic interventions targeting APP dysregulation remains an active area of research.

Are there any genetic mutations or variants associated with the APP gene?

Yes, mutations or variations in the APP gene have been identified in some familial forms of Alzheimer's disease. These mutations can increase the production or accumulation of amyloid-beta plaques, leading to an earlier onset and more aggressive form of the disease.

How is the expression or processing of APP protein regulated?

The expression and processing of APP protein are regulated by various mechanisms. Transcriptional regulation plays a role in controlling APP expression, where different transcription factors can influence its production. Moreover, post-translational modifications, such as phosphorylation and glycosylation, can affect APP processing pathways. Enzymes involved in APP cleavage, including beta-secretase (BACE1) and gamma-secretase, are also regulated and can influence the generation of amyloid-beta.

How is the APP protein associated with Alzheimer's disease?

In Alzheimer's disease, the APP protein undergoes abnormal processing, leading to the production and accumulation of amyloid-beta (Aβ) plaques in the brain. These plaques are a hallmark feature of the disease and are believed to contribute to neurodegeneration and cognitive decline.