Evidence map›Paper›PMID 22491959›Full record

ArticleActa neuropathologica2012

Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human α-synuclein under oligodendrocyte promoter: implications for multiple system atrophy.

Nadia Stefanova, Walter A Kaufmann, Christian Humpel, Werner Poewe, Gregor K Wenning

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

Article in Acta neuropathologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Cerebrospinal fluid levels of neurofilament light chain in multiple system atrophy relative to Parkinson's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017
    Pooled it
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  10. A Mouse Model of Multiple System Atrophy: Bench to Bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
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  17. Neurons and Glia Interplay in α-Synucleinopathies.International journal of molecular sciences · 2021
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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

5 authors at 1 institution in 1 country.

Nadia StefanovaDivision of Neurobiology, Innsbruck Medical University, Innsbruck, Austria. nadia.stefanova@i-med.ac.at
Walter A Kaufmann
Christian Humpel
Werner Poewe
Gregor K Wenning
Innsbruck Medical University · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple system atrophy (MSA) is a progressive late onset neurodegenerative α-synucleinopathy with unclear pathogenesis. Recent genetic and pathological studies support a central role of α-synuclein (αSYN) in MSA pathogenesis. Oligodendroglial cytoplasmic inclusions of fibrillar αSYN and dysfunction of the ubiquitin-proteasome system are suggestive of proteolytic stress in this disorder. To address the possible pathogenic role of oligodendroglial αSYN accumulation and proteolytic failure in MSA we applied systemic proteasome inhibition (PSI) in transgenic mice with oligodendroglial human αSYN expression and determined the presence of MSA-like neurodegeneration in this model as compared to wild-type mice. PSI induced open field motor disability in transgenic αSYN mice but not in wild-type mice. The motor phenotype corresponded to progressive and selective neuronal loss in the striatonigral and olivopontocerebellar systems of PSI-treated transgenic αSYN mice. In contrast no neurodegeneration was detected in PSI-treated wild-type controls. PSI treatment of transgenic αSYN mice was associated with significant ultrastructural alterations including accumulation of fibrillar human αSYN in the cytoplasm of oligodendroglia, which resulted in myelin disruption and demyelination characterized by increased g-ratio. The oligodendroglial and myelin pathology was accompanied by axonal degeneration evidenced by signs of mitochondrial stress and dysfunctional axonal transport in the affected neurites. In summary, we provide new evidence supporting a primary role of proteolytic failure and suggesting a neurodegenerative pathomechanism related to disturbed oligodendroglial/myelin trophic support in the pathogenesis of MSA.

Indexed as

2',3'-Cyclic-Nucleotide Phosphodiesterasesalpha-SynucleinAnalysis of VarianceAnimalsAutophagyBrainDopamine and cAMP-Regulated Phosphoprotein 32Exploratory BehaviorHumansMiceMice, Inbred C57BLMice, TransgenicMicroscopy, ImmunoelectronMotor ActivityMyelin Proteolipid ProteinNeurodegenerative Diseases2',3'-Cyclic-Nucleotide Phosphodiesterasesalpha-Synucleinbenzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinalDopamine and cAMP-Regulated Phosphoprotein 32Myelin Proteolipid ProteinOligopeptidesProteasome Endopeptidase ComplexTyrosine 3-MonooxygenaseUbiquitin

Identifiers

PMID22491959
PMCPMC3377902
OpenAlexW1972647893

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.