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Extracellular Deposition (extracellular + deposition)
Selected AbstractsAnatamopathological spectrum of tauopathiesMOVEMENT DISORDERS, Issue S6 2003Tamas Revesz MD Abstract The presence of tau-positive intraneuronal filamentous inclusions with or without additional inclusions in glial cells has been recognised as a major neuropathological feature in a significant group of neurodegenerative diseases, which are described as tauopathies. In one category of such diseases, the neuronal inclusions occur in association with extracellular deposition of a second aggregated protein (secondary tauopathies), whereas in another, the filamentous inclusions composed of tau are the sole neuropathological abnormality (primary tauopathies). Genetic studies of tauopathies in general, and in frontotemporal dementia with parkinsonism linked to chromosome 17 in particular, have significantly contributed to our knowledge about the pathogenesis not only of rare hereditary conditions but also of other more common diseases such as Alzheimer's disease and progressive supranuclear palsy. © 2003 Movement Disorder Society [source] The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau proteinNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2004S. Taniguchi Pathological examinations, using a panel of tau and other antibodies, were performed on the brains from 55 consecutively acquired cases of frontotemporal lobar degeneration (FTLD). Clinically, these comprised 31 cases of frontotemporal dementia (FTD), 10 cases of motor neurone disease inclusion dementia (MNDID), seven cases of progressive aphasia (PA), four cases of semantic dementia (SD) and three cases of progressive apraxia (PAX). Tau pathology, in the form of neurofibrillary tangles (NFTs) and glial cell tangles, was present in six cases of FTD with parkinsonism linked to chromosome 17, five of these cases resulting from +16 splice-site mutation and one from +13 mutation in the tau gene. The insoluble tau proteins were comprised mostly of four-repeat (4-R) isoforms. Eight other cases of FTD, one of PA and all three cases of PAX showed tau-positive inclusions (Pick bodies) and swollen cells (Pick cells), characteristic of Pick's disease. In these cases, the insoluble tau proteins were present in most instances as three-repeat (3-R) tau isoforms, although two cases with a mixture of 3-R and 4-R isoforms were seen. One other case of FTD showed an unusual pathology characterized by massive extracellular deposition of tau protein, composed of 4-R tau isoforms, within white matter without neuronal or glial cell inclusions. However, 33 (60%) of 55 FTLD cases showed no tau pathology in the brain, except for the rare NFTs, composed of a mix of 3-R and 4-R isoforms, in some of the more elderly cases. Of these 33 cases, 13 had FTD, 10 had MNDID, six had PA and four had SD. The pathological changes present were those of a superficial cortical laminar microvacuolation with mild subpial and subcortical gliosis; the 10 MNDID cases had ubiquitin-positive inclusions in the cerebral cortex and hippocampus. These 33 nontau FTLD cases, along with five Alzheimer's disease (AD) and six Huntington's disease (HD) cases with severe pathology, showed a variable loss of soluble tau proteins, broadly comparable with the extent of neuronal loss from the cortex and loss of the intracortical perikaryal marker, NeuN, but unrelated to proteins within afferent projection fibres such as neurofilament and ,-synuclein. Levels of tau mRNA were decreased in parallel in the tau-negative FTLD cases and in the severe AD and HD cases. Hence, the loss of tau from these 33 nontau FTLD cases is just one aspect of a neurodegenerative process that destroys many components of the nerve cell machinery and does not represent a specific disordering of the cell's ability to form tau proteins or incorporate these into microtubules. [source] Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in human mammary adenocarcinomas in vitro and in vivo,APMIS, Issue 6 2007SUSANNE MAUEL Transforming growth factor beta (TGF-ß) is able to inhibit proliferation of epithelial cells and is involved in the carcinogenesis of human mammary tumours. Three latent transforming growth factor-ß binding proteins (LTBP-1, -3 and -4) are involved in TGF-ß function. The aim of the study was to analyze the expression profiles of TGF-ß 1 and 2 and LTBP-4 in human mammary carcinoma cell lines as well as in human mammary tumours. Expression analysis was performed at the transcription and protein level under in vivo and in vitro conditions. LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary gland and in healthy mammary tissues of the same patients. Downregulation of LTBP-4 in all investigated human mammary tumours compared to normal tissues could be demonstrated. Results also revealed that protein levels of TGF-ß 1 are downregulated and of TGF-ß 2 are upregulated in human mammary carcinoma cell lines compared to primary (normal) human mammary epithelial cells. LTBP-4 reduction in neoplasms leads to a possible decrease of TGF-ß 1 extracellular deposition with reduced TGF-ß 1 bioavailability. TGF-ß 2 was upregulated, which indicates a possible compensatory mechanism. This study demonstrated a possible functional role of LTBP-4 for TGF-ß bioavailability with respect to carcinogenesis of human mammary tumours in vivo and in vitro. [source] Antifibrillizing agents catalyze the formation of unstable intermediate aggregates of beta-amyloidBIOTECHNOLOGY PROGRESS, Issue 4 2010Min S. Wang Abstract Although Alzheimer's disease (AD) is characterized by the extracellular deposition of fibrillar aggregates of beta-amyloid (A,), transient oligomeric species of A, are increasingly implicated in the pathogenesis of AD. Natively unfolded monomeric A, can misfold and progressively assemble into fibrillar aggregates, following a well-established "on pathway" seeded-nucleation mechanism. Here, we show that three simple saccharides, mannose, sucrose, and raffinose, alter A, aggregation kinetics and morphology. The saccharides inhibit formation of A, fibrils but promote formation of various oligomeric aggregate species through different "off pathway" aggregation mechanisms at 37°C but not at 60°C. The various oligomeric A, aggregates formed when coincubated with the different saccharides are morphologically distinct but all are toxic toward SH-SY5Y human neuroblastoma cells, increasing the level of toxicity and greatly prolonging toxicity compared with A, alone. As a wide variety of anti-A, aggregation strategies are being actively pursued as potential therapeutics for AD, these studies suggest that care must be taken to ensure that the therapeutic agents also block toxic oligomeric A, assembly as well as inhibit fibril formation. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] | ||||||||||