Online citations, reference lists, and bibliographies.
← Back to Search

Molecular Mechanisms Underlying Initiation Of Amyloid Fibril Formation

K. Yanagisawa
Published 2001 · Chemistry

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Deposition of aggregated amyloid β-protein (Aβ), a proteolytic cleavage product of the amyloid precursor protein (APP), is a fundamental pathological event in the development of Alzheimer’s disease (AD) [1]. Although a great deal of effort has been made to clarify the pathogenesis of AD, we are still far from a complete understanding of the molecular mechanism underlying the initiation of amyloid fibril formation. In regard to the mechanism of protein aggregation, the nucleation-dependent polymerization theory is widely accepted [2]. In this model, a long lag-time is required for nucleation. Furthermore, the concentration of a given protein is required to be greater than a critical level for nucleation. In regard to the polymerization of Aβ in vitro,Aβ at concentrations below 20 μM is unlikely to aggregate spontaneously. Considering that the physiological concentration of Aβ in biological fluids, including the cerebrospinal fluid, sera and culture media, is as low as 10 nM, even in the case of the expression of some genes responsible for familial AD which could induce increased generation of Aβ [3–6], one would assume that Aβ probably aggregates in brains in the presence of pathological chaperones such as apolipoprotein E4, α1-antichymotrypsin and proteoglycans. Alternatively, a pathological Aβ species with the ability to act as a seed or a template for fibril formation could be generated via a conformational alteration of Aβ, as has been postulated for the development of prion diseases [7]. In this chapter, I describe two novel Aβspecies with seeding ability, which were identified in the brains with AD or in culture media in our studies [8–10].
This paper references
10.1038/360672A0
Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production
M. Citron (1992)
10.1126/SCIENCE.8424174
Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
X. Cai (1993)
10.1016/0092-8674(93)90635-4
Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie?
J. Jarrett (1993)
10.1146/ANNUREV.CB.10.110194.002105
Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease.
D. Selkoe (1994)
10.1073/PNAS.91.4.1564
Polarized secretion of beta-amyloid precursor protein and amyloid beta-peptide in MDCK cells.
C. Haass (1994)
10.1126/SCIENCE.8191290
An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.
N. Suzuki (1994)
10.1038/NM1095-1062
GM1 ganglioside–bound amyloid β–protein (Aβ): A possible form of preamyloid in Alzheimer's disease
K. Yanagisawa (1995)
10.1083/JCB.128.4.537
Polarized sorting of beta-amyloid precursor protein and its proteolytic products in MDCK cells is regulated by two independent signals
C. Haass (1995)
10.1083/JCB.129.1.121
Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform [published erratum appears in J Cell Biol 1995 Jul;130(2):501]
A. Taraboulos (1995)
10.1016/0014-5793(95)00616-H
Intracellular lipid heterogeneity caused by topology of synthesis and specificity in transport. Example: sphingolipids
A. V. Helvoort (1995)
10.1074/JBC.271.43.26482
Membrane Disruption by Alzheimer β-Amyloid Peptides Mediated through Specific Binding to Either Phospholipids or Gangliosides
J. McLaurin (1996)
10.1038/nm0896-864
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
D. Scheuner (1996)
10.1046/j.1471-4159.1996.66041717.x
Increasing Age Alters Transbilayer Fluidity and Cholesterol Asymmetry in Synaptic Plasma Membranes of Mice
U. Igbavboa (1996)
10.1126/SCIENCE.278.5336.245
Prion diseases and the BSE crisis.
S. Prusiner (1997)
10.1038/42408
Functional rafts in cell membranes
K. Simons (1997)
10.1016/S0014-5793(96)01504-9
The interaction between Alzheimer amyloid β(1–40) peptide and ganglioside GM1‐containing membranes
L. Choo-Smith (1997)
10.1074/jbc.272.10.6324
Characterization of Detergent-insoluble Complexes Containing the Cellular Prion Protein and Its Scrapie Isoform*
N. Naslavsky (1997)
10.1074/jbc.272.37.22987
Acceleration of Amyloid Fibril Formation by Specific Binding of Aβ-(1–40) Peptide to Ganglioside-containing Membrane Vesicles*
L. P. Choo-Smith (1997)
10.1046/J.1471-4159.1997.69041661.X
Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins.
U. Igbavboa (2002)
10.1021/BI981843U
The presence of amyloid beta-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells.
M. Morishima-kawashima (1998)
10.1038/NM0698-730
A detergent-insoluble membrance compartment contains Aβ in vivo
Seungjae Lee (1998)
10.1016/S0005-2736(98)00097-2
Cholesterol-dependent generation of a unique amyloid beta-protein from apically missorted amyloid precursor protein in MDCK cells.
T. Mizuno (1998)
10.1021/BI982345O
Interactions of amyloid beta-peptide (1-40) with ganglioside-containing membranes.
K. Matsuzaki (1999)
10.1074/jbc.274.21.15110
Cholesterol-dependent Generation of a Seeding Amyloid β-Protein in Cell Culture*
Tetsuya Mizuno (1999)



Semantic Scholar Logo Some data provided by SemanticScholar