The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
Manipulating the amyloid-beta aggregation pathway with chemical chaperones.
D S Yang; C M Yip; T H Huang; A Chakrabartty; P E Fraser (Profiled Author: Fraser, Paul E)
Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada.
The Journal of biological chemistry 1999;274(46):32970-4.
Amyloid-beta (Abeta) assembly into fibrillar structures is a defining characteristic of Alzheimer's disease that is initiated by a conformational transition from random coil to beta-sheet and a nucleation-dependent aggregation process. We have investigated the role of organic osmolytes as chemical chaperones in the amyloid pathway using glycerol to mimic the effects of naturally occurring molecules. Osmolytes such as the naturally occurring trimethylamine N-oxide and glycerol correct folding defects by preferentially hydrating partially denatured proteins and entropically stabilize native conformations and polymeric states. Trimethylamine N-oxide and glycerol were found to rapidly accelerate the Abeta random coil-to-beta-sheet conformational change necessary for fiber formation. This was accompanied by an immediate conversion of amorphous unstructured aggregates into uniform globular and possibly nucleating structures. Osmolyte-facilitated changes in Abeta hydration also affected the final stages of amyloid formation and mediated transition from the protofibrils to mature fibers that are observed in vivo. These findings suggest that hydration forces can be used to control fibril assembly and may have implications for the accumulation of Abeta within intracellular compartments such as the endoplasmic reticulum and in vitro modeling of the amyloid pathway.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
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NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Total Funding: $ 3,600,812
TEPLOW, DAVID B.
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NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
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T H Huang; D S Yang; N P Plaskos; S Go; C M Yip; P E Fraser; A ChakrabarttyJournal of molecular biology 2000;297(1):73-87.
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