Evidence map›Paper›PMID 22137893›Full record

ArticleFree radical biology & medicine2012

Hydroxynonenal-generated crosslinking fluorophore accumulation in Alzheimer disease reveals a dichotomy of protein turnover.

Xiongwei Zhu, Rudy J Castellani, Paula I Moreira, Gjumrakch Aliev, Justin C Shenk, Sandra L Siedlak, Peggy L R Harris, Hisashi Fujioka, Lawrence M Sayre, Pamela A Szweda and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 2 countries.

Xiongwei ZhuDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address: xiongwei.zhu@case.edu.
Rudy J CastellaniDepartment of Pathology, University of Maryland, Baltimore, Maryland, USA.
Paula I MoreiraCenter for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Gjumrakch AlievInstitute for Neuroscience, University of Texas at San Antonio, San Antonio, Texas, USA.
Justin C ShenkInstitute for Neuroscience, University of Texas at San Antonio, San Antonio, Texas, USA.
Sandra L SiedlakDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Peggy L R HarrisDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Hisashi FujiokaDepartment of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
Lawrence M SayreDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio, USA.
Pamela A SzwedaDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Luke I SzwedaFree Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Mark A SmithDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
George PerryInstitute for Neuroscience, University of Texas at San Antonio, San Antonio, Texas, USA. Electronic address: george.perry@utsa.edu.
Case Western Reserve University · USThe University of Texas at San Antonio · USOklahoma Medical Research Foundation · USUniversity of Coimbra · PTUniversity of Maryland, Baltimore · USUniversity of Oklahoma Health Sciences Center · US

Funding

RCMI Center for Interdiscplinary Health Research CIHRG12MD007591 · NIMHD · UNIVERSITY OF TEXAS SAN ANTONIO · PI PERRY, GEORGE · 2012 to 2016
$10.4M
CYTOSKELETAL OXIDATIVE MODIFICATIONSR01AG014249 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI ANDERSON, VERNON E. · 1997 to 2004
$1.3M
NIA NIH HHS R01 AG014249NIA NIH HHS R01 AG14249NIMHD NIH HHS G12 MD007591
6 · The paper itself

Abstract

Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently bind amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated in intimate association with the pathological lesions of Alzheimer disease (AD), suggesting that oxidative stress is a major component of AD pathogenesis. Some HNE-protein products result in protein crosslinking through a fluorescent compound similar to lipofuscin, linking lipid peroxidation and the lipofuscin accumulation that commonly occurs in post-mitotic cells such as neurons. In this study, brain tissue from AD and control patients was examined by immunocytochemistry and immunoelectron microscopy for evidence of HNE-crosslinking modifications of the type that should accumulate in the lipofuscin pathway. Strong labeling of granulovacuolar degeneration (GVD) and Hirano bodies was noted but lipofuscin did not contain this specific HNE-fluorophore. These findings directly implicate lipid crosslinking peroxidation products as accumulating not in the lesions or the lipofuscin pathways, but instead in a distinct pathway, GVD, that accumulates cytosolic proteins.

Indexed as

Lipid PeroxidationProtein Processing, Post-TranslationalAdolescentAdultAgedAged, 80 and overAldehydesAlzheimer DiseaseBrainCase-Control StudiesCytoplasmic GranulesHumansLipofuscinMicroscopy, ImmunoelectronMiddle AgedNerve Tissue Proteins4-hydroxy-2-nonenalAldehydesLipofuscinNerve Tissue Proteins

Identifiers

PMID22137893
PMCPMC3268699
OpenAlexW2007035089

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.