Evidence map›Paper›PMID 28255164›Full record

ArticleScientific reports2017

Cholesterol impairment contributes to neuroserpin aggregation.

Costanza Giampietro, Maria Chiara Lionetti, Giulio Costantini, Federico Mutti, Stefano Zapperi, Caterina A M La Porta

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

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  8. Neuroserpin: structure, function, physiology and pathology.Cellular and molecular life sciences : CMLS · 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

6 authors at 3 institutions in 2 countries.

Costanza GiampietroFIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Maria Chiara LionettiCenter for Complexity and Biosystems, Department of Biosciences, University of Milano, via Celoria 26, 20133 Milano, Italy.
Giulio CostantiniCenter for Complexity and Biosystems, Department of Physics, University of Milano, via Celoria 16, 20133 Milano, Italy.
Federico MuttiCenter for Complexity and Biosystems, Department of Biosciences, University of Milano, via Celoria 26, 20133 Milano, Italy.
Stefano ZapperiCenter for Complexity and Biosystems, Department of Physics, University of Milano, via Celoria 16, 20133 Milano, Italy.
Caterina A M La PortaCenter for Complexity and Biosystems, Department of Biosciences, University of Milano, via Celoria 26, 20133 Milano, Italy.
University of Milan · ITFIRC Institute of Molecular Oncology · ITInstitute of Condensed Matter Chemistry and Technologies for Energy · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer's and Parkinson's diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

Indexed as

Protein AggregatesProtein Aggregation, PathologicalBetulinic AcidCholesterolCytoplasmic VesiclesFluorescent Antibody TechniqueGene ExpressionHeLa CellsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntracellular SpaceModels, TheoreticalNeuronsNeuropeptidesNeuroserpinProtein TransportbetulinBetulinic AcidCholesterolHydroxymethylglutaryl-CoA Reductase InhibitorsNeuropeptidesNeuroserpinProtein AggregatesSerpinsSterol Regulatory Element Binding Protein 1Sterol Regulatory Element Binding Protein 2Triterpenes

Identifiers

PMID28255164
PMCPMC5334643
OpenAlexW2592526703

What OpenQuestion holds

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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.