Non-Fucosylated Anti-Human Amyloid beta (AAB-002) Therapeutic Antibody (CAT#: BioBet-1616ZP) Datasheet

Aβ or Abeta

Amyloid beta; Beta amyloid peptide

Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients. The peptides result from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers (known as "seeds") can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The seeds or the resulting amyloid plaques are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.

Aβ; Abeta; Amyloid beta; Beta amyloid peptide

Plasma membrane, Extracellular region or secreted, Endosome, Nucleus

Diseases associated with APP include Cerebral Amyloid Angiopathy, App-Related and Alzheimer Disease.

Its related pathways are Neuroscience and Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways.

As a cell surface receptor, it performs physiological functions related to neurite growth, neuron adhesion, and axon formation on the surface of neurons. The interaction between APP molecules on adjacent cells promotes synapse formation. Participate in cell migration and transcription regulation through protein interactions. It promotes transcription activation by binding to APBB1-KAT5, and inhibits Notch signaling by interacting with numbness. Combined with G(O) and JIP-mediated apoptosis induction pathway. Inhibition of G(o)-atp enzyme activity (through similarity). As a kind of kinin I membrane receptor, it mediates the axonal transport of secretase and early protein 1 (similar). By acting as a kinesin I membrane receptor, it plays a role in the anterograde transport of axons to synapes. Participate in copper homeostasis/oxidative stress through the reduction of copper ions. In in vitro experiments, copper metallized APP directly induced neuronal death or enhanced neuronal death through Cu(2+)-mediated low-density lipoprotein oxidation. The growth of neurites can be regulated by combining with extracellular matrix components such as heparin, collagen I and IV. The splice isoform containing the BPTI domain has protease inhibitor activity. Inducing an age-dependent pathway involving activation of p38 MAPK, leading to amyloid-peptide internalization, leading to mitochondrial dysfunction in cultured cortical neurons. GPC1 is provided with copper (2+) ions, which are used to release nitric oxide (NO) and subsequently degrade the heparin sulfate chain on GPC1.

Neuroscience antibody

Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid beta proteins, amyloid-beta 40 (Abeta40) and amyloid-beta 42 (Abeta42), major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). Many other minor beta-amyloid peptides, beta-amyloid 1-X peptides, are found in cerebral spinal fluid (CSF) including the beta-amyloid X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686. Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either caspase-6, -8 or -9 results in the production of the neurotoxic C31 peptide and the increased production of beta-amyloid peptides. N- and O-glycosylated. O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short beta-amyloid peptides (beta-amyloid 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on beta-amyloid 38, beta-amyloid 40 nor on beta-amyloid 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate. Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific. Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins. Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta. The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members. Phosphorylation on Tyr-757 is required for SHC binding. Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin. Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of beta-amyloid-containing peptides. Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP). Beta-amyloid peptides are degraded by IDE.

Protein Based Therapies
Monoclonal antibody (mAb)

IgG

AAB-002

Humanized

Human

Bapineuzumab (AAB-001) that binds to beta amyloid peptide in the brainis is an experimental humanized monoclonal antibody, and it is being studied as a potential treatment for mild to moderate Alzheimer's disease.

Alzheimer's Disease

Alzheimer's Disease