Research Papers on Beta amyloid Sources:
Title: Platelets Are the Primary Source of Amyloid β-Peptide in Human Blood
Authors: Chen M., Inestrosa N. C., Ross G. S. and Fernandez H. L.
Abstract
The main component of Alzheimer′s disease (AD) amyloid deposits is amyloid β-peptide (Aβ), a fragment of the larger amyloid precursor protein (APP). The cellular source of Aβ is not known, but a circulatory origin has been postulated. We studied human blood from healthy individuals and found that platelets account for almost 90% of the total anti-Aβ immunoreactivity detected in whole blood. Using reverse-phase HPLC, we identified a platelet peptide which corresponds to Aβ by three criteria. (a) it shares a retention time with the synthetic Aβ1-40 peptide in two consecutive HPLC tests; (b) it interacts with two anti-Aβ antibodies in separate ELISAs; and, (c) its partial N-terminal amino acid sequence closely matches that of Aβ. The detection of this peptide in platelets indicates that, aside from the well-known non-amyloidogenic (secretory) pathway, the processing of APP in platelets from healthy individuals also involves an amyloidogenic pathway. These findings are consistent with the view that platelets are one of the major sources of Aβ in the circulation.
Title: In vitro expression analysis shows that the secretory form of gelsolin is the sole source of amyloid in gelsolin-related amyloidosis
Authors: H Kangas, T Paunio, N Kalkkinen, A Jalanko and L Peltonen
Abstract
Amyloidoses are a group of diseases where abnormal fibrillar protein deposits accumulate in patients' tissues. In familial amyloidosis of the Finnish type (FAF), or gelsolin-related amyloidosis, the amyloid subunit protein consists of gelsolin peptides of amino acids 173-243 with the disease causing substitution at Asp187. Gelsolin is an actin- modulating protein and exists in both secretory and intracellular forms both encoded by a single gene in chromosome 9. We have previously shown that the FAF-associated forms of secretory gelsolin carrying the Asp187Asn or Asp187Tyr mutations are abnormally processed in cells, resulting in the secretion of an aberrant 68 kDa carboxyterminal fragment. Here we demonstrate by N-terminal sequencing that the amino terminus of this abnormal fragment is the amino acid 173 and thus represents the N-terminus of the FAF amyloid. We also provide evidence that the same truncated gelsolin can be found among the aberrant gelsolin fragments detected in patients' CSF. Finally, we also expressed the FAF-associated forms of intracellular gelsolin in COS-1 cells, and found no abnormality in their processing opposite to secretory form. Our results provide strong evidence that the secretory gelsolin is solely responsible for the amyloid formation in FAF.
Title: Alzheimer’s amyloid peptide as a source of neurotoxic free radicals: the role of structural effects
Author: Dariusz Pogocki
Abstract.
This mini review gives a brief overview over the oxidation
mechanism of methionine (Met), relevant for processes which may lead to the
oxidation of amyloid -Beta peptide (BetaAP), involved in the pathogenesis of
Alzheimer’s disease. The CuII-catalysed oxidation of C-terminal Met35 in BetaAP
depends on the secondary structure of the peptide. That seems to be the key to
the known propensities of this peptide to form reactive oxygen species and
free radicals. The pro-oxidant character of BetaAP is not associated with its
Beta-sheet insoluble form. On the contrary, the alpha-helically organised structure is responsible for BetaAP redox-related cytotoxicity.
Title: Identification of full length β-amyloid precursor protein in human neuronal and non-neuronal cell culture supernatant: a possible extracellular source for the generation of Aβ
Authors: Kelly J. Conn a; Gregoris Papastoitsis b; Barbara Meckelein a; Carmela R. Abraham a
Abstract
β protein (Aβ) which is deposited in the amyloid plaques and vasculature in brains of Alzheimer's Disease (AD) patients is a 39 to 43 amino acid peptide proteolytically derived from the amyloid precursor protein (AβPP). Three major isoforms are expressed in the brain: AβPP751 and AβPP770 which contain a Kunitz-like protease inhibitor domain (KPI), and AβPP695 To date it is still unknown which AβPP isoforms are the precursors of Aβ, which proteolytic pathways are involved in its production, and if the processing occurs intracellularly and/or extracellularly. We now report the identification, by Western blot analysis, of an Aβ-containing AβPP protein which co-migrates with full length recombinant AβPP751 in the culture supernatant of two human neuroblastoma cell lines and in one human kidney cell line. This protein is recognized with six different antibodies towards AβPP targeting intracellular, extracel lular, and the Aβ region of AβPP. The immunodetection of this Aβ precursor is shown to be specific by absorption. The presence of full length AβPP in culture supernatant strongly suggests that some processing of ApPP may occur extracellularly. The recent identification of two soluble and/ or secreted proteases from AD and monkey brain both capable of processing recombinant AβPP in vitro1,2 suggests that Aβ production may occur extracellularly in vivo by an undescribed mechanism.
Chondrocyte of rheumatoid arthritis serve as a source of intra-articular acute-phase serum amyloid A protein
Authors: Shigeki Momohara Hiroshi Okamoto and Hisashi Yamanaka
Abstract: Article Outline
Title: On the uniform source of amyloid in plaques, tangles and vascular deposits
Authors: D. Carleton Gajdusek
Abstract
A series of recent studies involving isolation, sequencing and cloning of a precursor protein of amyloid of AD, as well as in aging and Guamanian ALS/PD confirms the unifying hypothesis that the amyloid of paired helical filaments, amyloid plaque cores and vascular amyloid are of one source. The gene for the precursor protein of this brain amyloid is on chromosome 21.
Source: PubMed
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