Evidence map›Paper›PMID 34556702›Full record

Observational studyScientific reports2021

Neuronal mitochondrial dysfunction in sporadic amyotrophic lateral sclerosis is developmentally regulated.

Tanisha Singh, Yuanyuan Jiao, Lisa M Ferrando, Svitlana Yablonska, Fang Li, Emily C Horoszko, David Lacomis, Robert M Friedlander, Diane L Carlisle

Open access · goldAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
4.0field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  3. Article
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  5. ALS-FTD-linked CCNFJournal of neuroinflammation · 2026
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  16. Regulation of Mutant Huntingtin Mitochondrial Toxicity by Phosphomimetic Mutations within Its N-Terminal Region.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
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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

9 authors at 3 institutions in 1 country.

Tanisha Singh *Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Yuanyuan Jiao *Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Lisa M FerrandoNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Svitlana YablonskaNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Fang LiNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Emily C HoroszkoNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
David LacomisDepartments of Neurology and Pathology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Robert M FriedlanderNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Diane L CarlisleNeuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh, B400 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. DLC4@pitt.edu.
Neurological Surgery · USPresbyterian Hospital · USUniversity of Pittsburgh · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyotrophic lateral sclerosis is an adult-onset neurodegenerative disorder characterized by loss of motor neurons. Mitochondria are essential for neuronal survival but the developmental timing and mechanistic importance of mitochondrial dysfunction in sporadic ALS (sALS) neurons is not fully understood. We used human induced pluripotent stem cells and generated a developmental timeline by differentiating sALS iPSCs to neural progenitors and to motor neurons and comparing mitochondrial parameters with familial ALS (fALS) and control cells at each developmental stage. We report that sALS and fALS motor neurons have elevated reactive oxygen species levels, depolarized mitochondria, impaired oxidative phosphorylation, ATP loss and defective mitochondrial protein import compared with control motor neurons. This phenotype develops with differentiation into motor neurons, the affected cell type in ALS, and does not occur in the parental undifferentiated sALS cells or sALS neural progenitors. Our work demonstrates a developmentally regulated unifying mitochondrial phenotype between patient derived sALS and fALS motor neurons. The occurrence of a unifying mitochondrial phenotype suggests that mitochondrial etiology known to SOD1-fALS may applicable to sALS. Furthermore, our findings suggest that disease-modifying treatments focused on rescue of mitochondrial function may benefit both sALS and fALS patients.

Indexed as

Cell DifferentiationAmyotrophic Lateral SclerosisBiopsyCells, CulturedFibroblastsHumansInduced Pluripotent Stem CellsMitochondriaMotor NeuronsNeural Stem CellsPrimary Cell CultureReactive Oxygen SpeciesSkinReactive Oxygen Species

Identifiers

PMID34556702
PMCPMC8460779
OpenAlexW3199583105

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.