Mapping the C terminal epitope of the Alzheimer's disease specific antibody MN423

Khuebachova, M; Verzillo, Vittorio; Škrabana, Rostislav; Ovečka, Milan; Vaccaro, Paola; Panni, Simona; Bradbury, Andrew; Novák, Michal

doi:10.1016/s0022-1759(02)00006-6

Cited by 19 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, it is certainly possible that proteolytic cleavage at amino acid 391 in AD recognized by the MN423 antibody 44 might eliminate TaunY394 reactivity, should it occur late in NFT evolution. Alternatively, phosphorylation at Y394 has previously been reported in AD, 45 and this may explain the limited nitration at this site.…”

Section: Timing Of Nitration During Tangle Evolution In Ad Pathogenesismentioning

confidence: 99%

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

Reyes

Vana

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

A substantial body of evidence suggests that nitrative injury contributes to neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative disorders. Previously, we showed in vitro that within the tau protein the N-terminal tyrosine residues (Y18 and Y29) are more susceptible to nitrative modifications than other tyrosine sites (Y197 and Y394). Using sitespecific antibodies to nitrated tau at Y18 and Y29, we identified tau nitrated in both glial (Y18) and neuronal (Y29) tau pathologies. In this study, we report the characterization of two novel monoclonal antibodies, Tau-nY197 and Tau-nY394, recognizing tau nitrated at Y197 and Y394, respectively. By Western blot analysis, Tau-nY197 labeled soluble tau and insoluble paired helical filament proteins (PHF-tau) nitrated at Y197 from control and AD brain samples. TaunY394 failed to label soluble tau isolated from control or severe AD samples, but labeled insoluble PHF-tau to a limited extent. Immunohistochemical analysis using Tau-nY197 revealed the hallmark tau pathology associated with AD; Tau-nY394 did not detect any pathological lesions characteristic of the disorder. These data suggest that a subset of the hallmark pathological inclusions of AD contain tau nitrated at Y197. However, nitration at Y197 was also identified in soluble tau from all control samples, including those at Braak stage 0, suggesting that nitration at this site in the proline-rich region of tau may have normal biological functions in the human brain.

show abstract

Section: Timing Of Nitration During Tangle Evolution In Ad Pathogenesismentioning

confidence: 99%

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

Reyes

Vana

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…to host cells is limited. New antibiotic, vaccine, and diagnostic targets are needed to prevent and treat infection by Listeria spp., and understanding the processes of adherence and entry into cells is fundamental to defining appropriate preventative and therapeutic strategies.Random peptide phage display has been successfully employed to identify new receptors and receptor ligands (44,52,53,82) and in epitope mapping and mimicking of protein antigens and antibodies (16,42,61) and drug discovery (40,52,78). In this study we employed random peptide phage display in an attempt to identify novel surface antigens that may be used as therapeutic targets and diagnostic markers for Listeria spp.…”

mentioning

confidence: 99%

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

et al. 2006

View full text Add to dashboard Cite

The gram-positive bacterium Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor CI M6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.The gram-positive bacterium Listeria monocytogenes is a human pathogen that causes listeriosis primarily in immunosuppressed individuals. Symptoms are flu-like, and yet disease may progress to severe complications such as meningitis, septicemia, spontaneous abortion, or listeriosis of the newborn (28,39,83). The number of cases of listeriosis range from 40 to 44 per year in Australia (3, 79) and average 100 per year in the United States (13). Although the incidence of listeriosis is low compared to that of other foodborne diseases, the associated mortality rate is high (approximately 30%) (39, 74, 83). Knowledge of the molecular mechanisms underlying the binding and internalization of Listeria spp. to host cells is limited. New antibiotic, vaccine, and diagnostic targets are needed to prevent and treat infection by Listeria spp., and understanding the processes of adherence and entry into cells is fundamental to defining appropriate preventative and therapeutic strategies.Random peptide phage display has been successfully employed to identify new receptors and receptor ligands (44,52,53,82) and in epitope mapping and mimicking of protein antigens and antibodies (16,42,61) and drug discovery (40,52,78). In this study we employed random peptide phage display in an attempt to identify novel surface antigens that may be used as therapeutic targets ...

show abstract

“…The MN423 has unequivocal specificity for tau ordered into the PHF structure (Khuebachova et al 2002;Skrabana et al 2004;Wischik et al 1988aWischik et al , 1988b and A 68 PHF1 Fig. 2 Expression of Alzheimer's tau in the rat brain induces complete tau cascade of neuropathology including the sarcosylinsoluble tau with the A68 triplet characteristic of human AD neurofibrillary degeneration.…”

Section: Structural Neuroproteomicsmentioning

confidence: 99%

New Age of Neuroproteomics in Alzheimer’s Disease Research

2009

View full text Add to dashboard Cite

Alzheimer's disease (AD) is the leading cause of dementia, a condition that gradually destroys brain cells and leads to progressive decline in mental functions. The disease is characterized by accumulation of misfolded neuronal proteins, amyloid and tau, into insoluble aggregates known as extracellular senile plaques and intracellular neurofibrillary tangles, respectively. However, only tau pathology appears to correlate with the progression of the disease and it is believed to play a central role in the progression of neurodegeneration. In AD, tau protein undergoes various types of posttranslational modifications, most notably hyperphosphorylation and truncation. Using four proteomics approaches we aimed to uncover the key steps leading to neurofibrillary degeneration and thus to identify therapeutic targets for AD. Functional neuroproteomics was employed to generate the first transgenic rat model of AD by expressing a truncated misordered form of tau, "Alzheimer's tau". The rat model showed that Alzheimer's tau toxic gain of function is responsible for the induction of abnormal tau cascade and is the driving force in the development of neurofibrillary degeneration. Structural neuroproteomics allowed us to determine partial 3D structure of the Alzheimer's filament core at a resolution of 1.6 A. Signaling neuroproteomics data lead to the identification and characterization of relevant phosphosites (the tau phosphosignalome) contributing to neurodegeneration. Interaction neuroproteomics revealed links to a new group of proteins interacting with Alzheimer's tau (tau interactome) under normal and pathological conditions, which would provide novel drug targets and novel biomarkers for treatment of AD and other tauopathies.

show abstract

Mapping the C terminal epitope of the Alzheimer's disease specific antibody MN423

Cited by 19 publications

References 30 publications

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

Tyrosine Nitration within the Proline-Rich Region of Tau in Alzheimer's Disease

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

New Age of Neuroproteomics in Alzheimer’s Disease Research

Contact Info

Product

Resources

About