Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pronounced neurodegeneration of hippocampal pyramidal neurons has been shown in Alzheimer's disease. The aim of this study was to establish an organotypic in vitro model for investigating effects of the amyloid beta (Abeta)-peptide on pyramidal neuron degeneration, glial cell activation and tau phosphorylation. Tissue cultures in a quasi-monolayer were obtained using roller-drum incubation of hippocampal slices from neonatal Sprague Dawley rats. Neuronal populations identified included N-methyl-D-aspartate (NMDA-R1) receptor immunoreactive pyramidal neurons, and neurons immunopositive for glutamic acid decarboxylase-65 (GAD65) or gamma amino butyric acid (GABA). Many neurons expressed phosphorylated tau as shown by pS(396), AD2 and PHF-tau immunostaining. Astrocytes, microglial cells and macrophages were also identified. The Abeta(25-35) peptide formed fibrillar networks within 2 days as demonstrated by electron microscopy. In the presence of the neurotoxic Abeta(25-35) peptide, but not Abeta(35-25), deposits developed in the tissue that were stainable with Thioflavine T and Congo red and showed the characteristic birefringence of Abeta plaques. Following Abeta(25-35) exposure, neurodegenerative cells were observed with Fluoro-Jade B staining. Further characterization of pyramidal neurons immunopositive for NMDA-R1 showed a decrease of cell number in the immediate surrounding of Abeta(25-35) deposits in a time- and concentration-dependent fashion. Similar effects on pyramidal neurons were obtained following exposure to the full-length, Abeta(1-40) peptide. Also, a loss of neuronal processes was seen with GAD65, but not GABA, immunohistochemistry after exposure to Abeta(25-35). Abeta(25-35)-exposed neurons immunopositive for phospho-tau showed degenerating, bent and often fragmented processes. Astrocytes showed increased GFAP-positive reactivity after Abeta(25-35) exposure and formation of large networks of processes. No obvious effect on microglial cells and macrophages could be seen after the Abeta(25-35) exposure. The developed in vitro system may constitute a useful tool for screening novel drugs against Abeta-induced alterations of tau and degeneration of hippocampal neurons.
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PMID:Modelling of amyloid beta-peptide induced lesions using roller-drum incubation of hippocampal slice cultures from neonatal rats. 1617 62

Although neurofibrillary tangles and senile plaques have been identified as the hallmark pathological changes in the brain of Alzheimer's disease (AD), the relationship between them is still not fully understood. In the present study, we have studied the effect of endogenously overproduced amyloid beta (A beta) on tau by using wild type amyloid precursor protein (APP) transfected (N2a/APP695), or Swedish mutant APP plus Delta 9 deleted presenilin-1 co-transfected (N2a/APPswe.Delta 9) and APP vector transfected (N2a/vector) cell lines. We measured the secreted and intracellular A beta, including A beta(1-40) and A beta(1-42), by Sandwich ELISA assay. It was shown that the levels of A beta were increased time-dependently in N2a/APP695 and N2a/APPswe.Delta 9 but not in N2a/vector upon butyric acid (BA) treatment. Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment. Obvious accumulation of the hyperphosphorylated tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was observed at 48 h after BA treatment. The total level of the extracted tau was reduced in N2a/APP695 and N2a/APPswe.Delta 9 lines compared with N2a/vector cells by Western blot, and this reduction of total tau was also detected by immunofluorescence staining. No obvious alteration of tau mRNA was observed in both N2a/APP695 and N2a/APPswe.Delta 9 cells compared with N2a/vector. This study provides direct evidence demonstrating that endogenously overproduced A beta not only induces tau hyperphosphorylation but also decreases the level and solubility of tau in N2a cell lines.
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PMID:Endogenous overproduction of beta-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells. 1675 46