Anti-Tau Antibody, Cleaved (D421), clone Tau-C3, Ascites Free

Microtubule-associated protein tau (UniProt P10636; also known as Neurofibrillary tangle protein, Paired helical filament-tau, PHF-tau) is encoded by the MAPT (also known as TAU, MAPT1, MTBTL) gene (Gene ID 4137) in human. Extracellular plaque deposits composed of amyloid-β and intracellular neurofibrillary tangles (NFTs) composed of truncated and hyperphosphorylated tau are two neuropathological hallmarks of Alzheimer′s disease (AD). Tau pathology (tauopathy) can cause toxicity when the brain is devoid of amyloid plaques, and tangle pathology correlates better with clinical dementia than amyloid pathology. Abnormal processing of tau by hyperphosphorylation and proteolytic truncation contribute to the toxicity of tau. Tau is known to be cleaved by various proteases, including caspases, calpains, cathepsins, thrombin, and puromycin-sensitive aminopeptidase, as well as the lysosomal cysteine proteinase asparagine endopeptidase (AEP). MAPK, GSK-3, and Cdk-5 are three known kinases that target various tau phosphorylation sites. Tau also undergoes other types of posttranslational modifications, including glycosylation, ubiquitination, glycation, polyamination, nitration, and lysine methylation, which are believed to be important for its non-pathological functions, including polymerization and stabilization of microtubules.

Variable, depending on the Tau isoforms where the fragments are derived from and whether the fragements were cleaved at the N-terminus by other proteases.

Epitope: C-terminus.

KLH-conjugated linear peptide corresponding to a human Tau sequence with Asp421 at the C-terminus.

Anti-Tau Antibody, Cleaved (D421), clone Tau-C3, Ascites Free is an antibody against Tau for use in Immunohistochemistry (Paraffin), Immunofluorescence, Western Blotting, Immunocytochemistry.

Immunofluorescence Analysis: A representative lot detected truncated Tau cleaved at D421 in the frontal cortex and hippocampus sections from rTg4510 mice expressing human P301L mutant Tau transgene (Ramalho, R.M., et al. (2008). Mol. Med. 14(5-6):309-317).
Immunofluorescence Analysis: A representative lots detected pathological tangles containing truncated Tau cleaved at D421 by fluorescent immunohistochemistry staining of Alzheimer′s diseased (AD) human brain sections (Guillozet-Bongaarts, A.L., et al. (2005). Neurobiol. Aging. 26(7):1015-1022; Horowitz, P.M., et al. (2004). J. Neurosci. 24(36):7895-7902).
Immunohistochemistry Analysis: A representative lot detected an increase of truncated Tau cleaved at D421 in the brain section from rTg4510 mice expressing human P301L mutant Tau transgene when compared with sections from non-transgenic mice (Ramalho, R.M., et al. (2008). Mol. Med. 14(5-6):309-317).
Immunohistochemistry Analysis: A representative lot immunostained neurofibrillary tangles (NFTs) and neuritic plaques (NPs) containing truncated Tau cleaved at D421 in frozen hippocampus sections from Alzheimer′s diseased (AD) human brains (Gamblin, T.C., et al. (2003). Proc. Natl. Acad. Sci. U. S. A. 100(17):10032-10037).
Western Blotting Analysis: A representative lot detected truncated Tau cleaved at D421 in frontal cortex and hippocampus tissue extracts from non-transgenic and rTg4510 transgenic mice with human P301L mutant Tau transgene (Ramalho, R.M., et al. (2008). Mol. Med. 14(5-6):309-317).
Western Blotting Analysis: A representative lots detected recombinantt Tau 1-421 fragment, but not 1-391 or 1-429 fragment or full-length Tau. Clone TauC3 detected tau fragment generated by caspase-mediated D421 cleavage of full-length recombinant Tau (Guillozet-Bongaarts, A.L., et al. (2005). Neurobiol. Aging. 26(7):1015-1022; Park, S.Y., and Ferreira, A. (2005). J. Neurosci. 25(22):5365-5375; Gamblin, T.C., et al. (2003). Proc. Natl. Acad. Sci. U. S. A. 100(17):10032-10037).
Immunocytochemistry Analysis: A representative lot detected a time-dependent increase of intracellular truncated Tau cleaved at D421 by fluorescent immunocytochemistry staining of paraformaldehyde-fixed primary embryonic rat cortical neurons subjected to fibrilar Aβ (1–42) treament (Gamblin, T.C., et al. (2003). Proc. Natl. Acad. Sci. U. S. A. 100(17):10032-10037).

Research Category
Neuroscience

Research Sub Category
Neurodegenerative Diseases

Clone Tau-C3 (TauC3) specifically recognizes caspase-cleaved Tau fragments with Asp421/D421 as the C-termus. Does not react with full-length Tau or Tau fragments with other cleaved C-termi. Uniprot P10636 lists 9 human tau isoforms produced by alternative splicing. The Asp421/D421 designation was based on D421 of isoform 8 (Tau-F, Tau-4), which is equivalent to D738 of isoform 1 (PNS-tau), D332 of isoform 2 (Fetal-tau), D296 of isoform 3 (Tau-A), D361 of isoform 4 (Tau-B), D390 of isoform 5 (Tau-C, Tau-3), D363 of isoform 6 (Tau-D), D392 of isoform 7 (Tau-E), and D756 of isoform 9 (Tau-G).

Format: Purified

Protein G Purified

Purified mouse monoclonal IgG1κ antibody in buffer containing 0.1 M Tris-Glycine (pH 7.4), 150 mM NaCl with 0.05% sodium azide.

Stable for 1 year at 2-8°C from date of receipt.

Evaluated by Immunohistochemistry in Alzheimer′s diseased (AD) human brain tissue .

Immunohistochemistry Analysis: An 1:250 dilution of this antibody detected Asp421-cleaved Tau in neurofibrillary tangles (NFTs) of Alzheimer′s diseased (AD) human brain tissue .

Concentration: Please refer to lot specific datasheet.

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