The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation.

The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Research Abstract Details 

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The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Abstract Text:

Sarah J Siegel,Jan Bieschke,Evan T Powers,Jeffery W Kelly,

4-Hydroxynonenal (4-HNE), formed as a consequence of oxidative stress, exists at increased concentrations in Alzheimer's disease (AD) patients and is found in amyloid beta peptide (Abeta) plaques associated with AD. Although it remains an open question as to whether oxidative stress is a causative factor or a consequence of AD, we show here that 4-HNE, putatively resulting from the peroxidation of lipids, covalently modifies Abeta, triggering its aggregation. These Abeta modifications result from 1,4 conjugate addition and/or Schiff base formation, they occur at multiple locations on a single Abeta peptide, and they result in covalent cross-linking of Abeta peptides. The consequence of these reactions is that 4-HNE accelerates the formation of Abeta protofibrils while inhibiting the production of straight, mature fibrils. Recent studies implicating Abeta oligomers and protofibrils in the neurotoxic process that ultimately leads to AD suggest that the Abeta aggregates induced by 4-HNE may be important in the pathogenesis of AD. These results provide further incentive to understand the role of oxidative stress and small-molecule Abeta modifications in sporadic AD.

The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Publishing Authors By Initials

SJ Siegel,J Bieschke,ET Powers,JW Kelly,

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The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 1503-10

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 13

MONTH: Feb

YEAR: 2007

The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Keywords Mesh Terms:

KEYWORDS: Spectrometry, Mass, Matrix-Assisted Lase

MESH TERMS: ultrastructure

Chemical & Substance for Abstract: The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Information

Substance Name: 4-hydroxy-2-nonenal

Registry Number: 29343-52-0

Grant and Affiliation Information for The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation.

AFFILIATION: The Scripps Research Institute, and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS 50636

ACRONYM: NS

MEDLINETA: Biochemistry

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