New method for determining size of critical nucleus of fibril formation of polypeptide chains

Protofibrillar trimer is the critical nucleus for the αS fibril formation, and the tetramer is the minimal stable nucleus. The interactions of DA/NE with αS trimer/tetramer disrupt the backbone H-bonds and destabilize the αS protofibrils.

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IS IT POSSIBLE TO PREDICT AMYLOIDOGENIC REGIONS FROM SEQUENCE ALONE?

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720006002004 ◽

2006 ◽

Vol 04 (02) ◽

pp. 373-388 ◽

Cited By ~ 19

Author(s):

OXANA V. GALZITSKAYA ◽

SERGIY O. GARBUZYNSKIY ◽

MICHAIL YU. LOBANOV

Keyword(s):

Amino Acid ◽

Protein Sequence ◽

Amyloid Fibrils ◽

Amyloid Fibril ◽

Fibril Formation ◽

Amino Acid Sequences ◽

Amyloid Formation ◽

Amyloid Fibril Formation ◽

Polypeptide Chains ◽

Proteins And Peptides

Identification of potentially amyloidogenic regions in polypeptide chains is very important because the amyloid fibril formation can be induced in most normal proteins. In our work we suggest a new method to detect amyloidogenic regions in protein sequence. It is based on the assumption that packing is tight inside an amyloid and therefore regions which could potentially pack well would have a tendency to form amyloids. This means that the regions with strong expected packing of residues would be responsible for the amyloid formation. We use this property to identify potentially amyloidogenic regions in proteins basing on their amino acid sequences only. Our predictions are consistent with known disease-related amyloidogenic regions for 8 of 11 amyloid-forming proteins and peptides in which the positions of amyloidogenic regions have been revealed experimentally. Predictions of the regions which are responsible for the formation of amyloid fibrils in proteins unrelated to disease have been also done.

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Immunocytochemical Localization of Amyloid Protein AA in the “Dense Fibrillar Inclusions” of the Reticuloendothelical Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079632 ◽

1977 ◽

Vol 35 ◽

pp. 438-439

Author(s):

T. Shirahama ◽

M. Skinner ◽

A.S. Cohen

Keyword(s):

Amyloid Fibril ◽

Close Association ◽

Gel Filtration ◽

Fibril Formation ◽

Amyloid Protein ◽

Electron Microscopic ◽

Amyloid Deposits ◽

Amyloid Fibril Formation ◽

Electron Microscopic Technique ◽

Lysosomal System

A1thought the mechanisms of amyloidogenesis have not been entirely clarified, proteolysis of the parent proteins may be one of the important steps in the amyloid fibril formation. Recently, we reported that "dense fibrillar inclusions" (DFI), which had the characteristics of lysosomes and contained organized fibrillar profiles as well, were observed in the reticuloendothelial cells in close association with the foci of new amyloid deposits. We considered the findings as evidence for the involvement of lysosomal system in amyloid fibril formation (l). In the present study, we attempted to determine the identity of the contents of the DFI by the use of antisera against the amyloid protein (AA) and an immuno-electron microscopic technique.Amyloidosis was induced in CBA/J mice by daily injections of casein (l). AA was isolated from amyloid-laden spleens by gel filtration and antibody to it was produced in rabbits (2). For immunocytochemistry, the unlabeled antibody enzyme method (3) was employed.

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Selective Sampling and Orientation of Non-Homogeneous Tissues

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100238 ◽

1968 ◽

Vol 26 ◽

pp. 98-99

Author(s):

C. C. Clawson ◽

L. W. Anderson ◽

R. A. Good

Keyword(s):

Electron Microscopy ◽

Electron Microscope ◽

Light Microscopy ◽

Random Sampling ◽

New Method ◽

Microscope Examination ◽

Small Areas ◽

Selective Sampling ◽

Large Numbers ◽

Specific Orientation

Investigations which require electron microscope examination of a few specific areas of non-homogeneous tissues make random sampling of small blocks an inefficient and unrewarding procedure. Therefore, several investigators have devised methods which allow obtaining sample blocks for electron microscopy from region of tissue previously identified by light microscopy of present here techniques which make possible: 1) sampling tissue for electron microscopy from selected areas previously identified by light microscopy of relatively large pieces of tissue; 2) dehydration and embedding large numbers of individually identified blocks while keeping each one separate; 3) a new method of maintaining specific orientation of blocks during embedding; 4) special light microscopic staining or fluorescent procedures and electron microscopy on immediately adjacent small areas of tissue.

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Ultrastructural analysis of collagen formation in the developing primate amnion

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158078 ◽

1990 ◽

Vol 48 (3) ◽

pp. 106-107

Author(s):

Barry F. King ◽

Grete N. Fry

Keyword(s):

Golgi Apparatus ◽

Collagen Fibril ◽

Fibril Formation ◽

Amniotic Cavity ◽

Cytological Evidence ◽

Mammalian Embryo ◽

Intracellular Location ◽

Collagen Formation ◽

Amniotic Epithelium ◽

Extraembryonic Mesoderm

The amnion surrounding the mammalian embryo consists of the amniotic epithelium facing the amniotic cavity, a layer of extraembryonic mesoderm bordering the exocoelom and an intervening layer of extracellular matrix (Fig. 1). During gestation the amnion expands remarkably to acommodate the rapidly growing embryo. In this study we have examined the process of collagen fibril formation in the developing amnion of the rhesus monkey between 20 and 60 days of gestation.Most cytological evidence of collagen fibril formation was observed in association with the extraembryonic mesodermal cells rather than the amniotic epithelium. The mesodermal cells h ad abundant cisternae of rough endoplasmic reticulum and a prominent Golgi apparatus. Elongated secretory vacuoles were associated with the Golgi apparatus and often contained parallel aggregates of fine filaments (Fig. 2). In some secretory vacuoles, periodic densities also were observed. Some striated collagen fibrils were observed in an apparent intracellular location in long, membrane-limited compartments (Fig. 3). Still other striated fibrils were observed in dense bodies, presumably lysosomes (Fig. 4).

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Insights into amyloid disease from fly models

Essays in Biochemistry ◽

10.1042/bse0560069 ◽

2014 ◽

Vol 56 ◽

pp. 69-83 ◽

Cited By ~ 1

Author(s):

Ko-Fan Chen ◽

Damian C. Crowther

Keyword(s):

Drosophila Melanogaster ◽

Neurodegenerative Disorders ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Disease Pathogenesis ◽

Amyloid Aggregates ◽

Aβ Amyloid ◽

Polypeptide Chains ◽

Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

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