Identification of a caspase-derived N-terminal tau fragment in cellular and animal Alzheimer's disease models
| Autor: | Nadia Canu, T.T. Rohn, Antonino Cattaneo, Pietro Calissano, Anna Atlante, Maria Teresa Cencioni, Veronica Corsetti, Antonietta Gentile, G. Amadoro, Simona Capsoni, M.T. Ciotti |
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| Přispěvatelé: | Corsetti, V, Amadoro, G, Gentile, A, Capsoni, Simona, Ciotti, Mt, Cencioni, Mt, Atlante, A, Canu, N, Rohn, Tt, Cattaneo, Antonino, Calissano, P. |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Caspase(s) Transgene Cellular differentiation caspase Amino Acid Motifs Neurotoxins Socio-culturale Mice Transgenic tau Proteins Settore BIO/09 Cellular and Molecular Neuroscience Mice Tau apoptosis Alzheimer caspase In vivo Alzheimer Disease Cell Line Tumor medicine Staurosporine Animals Humans Enzyme Inhibitors Neurodegeneration Molecular Biology Caspase biology apoptosis tau proteolysis caspase(s) Alzheimer's disease neurodegeneration Cell Differentiation Cell Biology medicine.disease Caspase Inhibitors Peptide Fragments Cell biology Disease Models Animal Biochemistry Caspases Proteolysis biology.protein Alzheimer Tau medicine.drug |
| Zdroj: | Molecular and cellular neurosciences 38 (2008): 381–392. doi:10.1016/j.mcn.2008.03.011 info:cnr-pdr/source/autori:Corsetti b; G. Amadoro a, b; A. Gentile a; S. Capsoni c; M.T. Ciotti c; M.T. Cencioni e; A. Atlante d; N. Canu a, b; T.T. Rohn f; A. Cattaneo b; P. Calissano a, b/titolo:Identification of a caspase-derived N-terminal tau fragment in cellular and animal Alzheimer's disease models/doi:10.1016%2Fj.mcn.2008.03.011/rivista:Molecular and cellular neurosciences (Print)/anno:2008/pagina_da:381/pagina_a:392/intervallo_pagine:381–392/volume:38 info:cnr-pdr/source/autori:Corsetti V., Amadoro G., Gentile A., Capsoni S.,Ciotti M.T., Cencion M.T.i,Atlante A., Canu N., Rohn T.T.,Cattaneo A., Calissano P./titolo:Identification of a caspase-derived n-terminal tau fragment in cellular and animal alzheimer disease models/doi:10.1016%2Fj.mcn.2008.03.011/rivista:Molecular and cellular neurosciences (Print)/anno:2008/pagina_da:381/pagina_a:392/intervallo_pagine:381–392/volume:38 |
| DOI: | 10.1016/j.mcn.2008.03.011 |
| Popis: | Biochemical modifications of tau proteins have been proposed to be among the earliest neurobiological changes in Alzheimer's disease (AD) and correlate better with cognitive symptoms than do beta-amyloid plaques. We have recently reported that adenovirus-mediated overexpression of the NH2 26-230aa tau fragment evokes a potent NMDA-mediated neurotoxic effect in primary neuronal cultures. In order to assess whether such N-terminal tau fragment(s) are indeed produced during apoptosis or neurodegeneration in vivo, we attempted to ascertain their presence in cell and animal models using an anti-tau antibody directed against the N-terminal sequence of human protein located downstream of the caspase(s)-cleavage site DRKD(25)-QGGYTMHQDQ. We provide biochemical evidence that a caspase(s)-cleaved NH2-terminal tau fragment of 20-22 kDa, consistent with the size of the NH2 26-230aa neurotoxic fragment of tau, is generated in vitro in differentiated human SH-SY5Y cells undergoing apoptosis by BDNF withdrawal or following treatment with staurosporine. In addition this NH2-terminally cleaved tau fragment, whose expression correlates with a significant up-regulation of caspase(s) activity, is also specifically detected in vivo in the hippocampus of 15 month-old AD11 transgenic mice, a model in which a progressive AD-like neurodegeneration is induced by the expression of transgenic anti-NGF antibodies. The results support the idea that aberrant activation of caspase(s), following apoptotic stimuli or neurodegeneration insults, may produce one or more toxic NH2 tau fragments, that further contribute to propagate and increase cellular dysfunctions in AD. |
| Databáze: | OpenAIRE |
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