Linked Life Data

14769048

Source:http://linkedlifedata.com/resource/pubmed/id/14769048

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-2-10
pubmed:abstractText
Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule-associated protein tau. In vitro, fibrillization of full-length, unphosphorylated recombinant tau can be induced under near-physiological conditions by treatment with various agents, including anionic surfactants. Here we examine the pathway through which anionic surfactants promote tau fibrillization using a combination of electron microscopy and fluorescence spectroscopy. Protein and surfactant first interacted in solution to form micelles, which then provided negatively charged surfaces that accumulated tau aggregates. Surface aggregation of tau protein was followed by the time-dependent appearance of a thioflavin S reactive intermediate that accumulated over a period of hours. The intermediate was unstable in the absence of anionic surfaces, suggesting it was not filamentous. Fibrillization proceeded after intermediate formation with classic nucleation-dependent kinetics, consisting of lag phase followed by the exponential increase in filament lengths, followed by an equilibrium phase reached in approximately 24 h. The pathway did not require protein insertion into the micelle hydrophobic core or conformational change arising from mixed micelle formation, because anionic microspheres constructed from impermeable polystyrene were capable of qualitatively reproducing all aspects of the fibrillization reaction. It is proposed that the progression from amorphous aggregation through intermediate formation and fibrillization may underlie the activity of other inducers such as hyperphosphorylation and may be operative in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1704-14
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14769048-Alzheimer Disease, pubmed-meshheading:14769048-Anions, pubmed-meshheading:14769048-Arachidonic Acid, pubmed-meshheading:14769048-Humans, pubmed-meshheading:14769048-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:14769048-Intermediate Filament Proteins, pubmed-meshheading:14769048-Micelles, pubmed-meshheading:14769048-Microspheres, pubmed-meshheading:14769048-Neurofibrillary Tangles, pubmed-meshheading:14769048-Neurofilament Proteins, pubmed-meshheading:14769048-Recombinant Proteins, pubmed-meshheading:14769048-Spectrometry, Fluorescence, pubmed-meshheading:14769048-Static Electricity, pubmed-meshheading:14769048-Surface Properties, pubmed-meshheading:14769048-Surface-Active Agents, pubmed-meshheading:14769048-Thiazoles, pubmed-meshheading:14769048-tau Proteins
pubmed:year
2004
pubmed:articleTitle
Evidence for an intermediate in tau filament formation.
pubmed:affiliation
Biophysics Program, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.