Evidence map›Paper›PMID 34518579›Full record

ArticleScientific reports2021

A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin.

Phaneendra Chennampally, Ambreen Sayed-Zahid, Prabakaran Soundararajan, Jocelyn Sharp, Gregory A Cox, Scott D Collins, Rosemary L Smith

Erratum issuedAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
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  11. Organ on a Chip: A NovelFrontiers in neurology · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Phaneendra Chennampally *Microinstruments and Systems Laboratory, University of Maine, Orono, ME, 04469, USA.
Ambreen Sayed-Zahid *Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, 04469, USA.
Prabakaran SoundararajanThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Jocelyn SharpThe Jackson Laboratory, Bar Harbor, ME, 04609, USA.
Gregory A CoxGraduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, 04469, USA. greg.cox@jax.org.
Scott D CollinsMicroinstruments and Systems Laboratory, University of Maine, Orono, ME, 04469, USA.
Rosemary L SmithMicroinstruments and Systems Laboratory, University of Maine, Orono, ME, 04469, USA.

Funding

Polyalanine Tails: A Novel Type of Protein Modification Implicated in NeurodegenerationR01NS102414 · NINDS · JACKSON LABORATORY · PI Robert W. Burgess, GREGORY A. COX · 2017 to 2026
$7.0M
Engineering the Development of Neuromuscular Circuitry On-ChipR15NS111377 · NINDS · UNIVERSITY OF MAINE ORONO · PI SMITH, ROSEMARY L. · 2019 to 2019
$435k
NINDS NIH HHS R01 NS102414NINDS NIH HHS R15 NS111377
6 · The paper itself

Abstract

TAR DNA-binding protein-43 (TDP-43) is known to accumulate in ubiquitinated inclusions of amyotrophic lateral sclerosis affected motor neurons, resulting in motor neuron degeneration, loss of motor functions, and eventually death. Rapamycin, an mTOR inhibitor and a commonly used immunosuppressive drug, has been shown to increase the survivability of Amyotrophic Lateral Sclerosis (ALS) affected motor neurons. Here we present a transgenic, TDP-43-A315T, mouse model expressing an ALS phenotype and demonstrate the presence of ubiquitinated cytoplasmic TDP-43 aggregates with > 80% cell death by 28 days post differentiation in vitro. Embryonic stem cells from this mouse model were used to study the onset, progression, and therapeutic remediation of TDP-43 aggregates using a novel microfluidic rapamycin concentration gradient generator. Results using a microfluidic device show that ALS affected motor neuron survival can be increased by 40.44% in a rapamycin dosage range between 0.4-1.0 µM.

Indexed as

MicrofluidicsAmyotrophic Lateral SclerosisAnimalsCell SurvivalDNA-Binding ProteinsMice, TransgenicMotor NeuronsMutationNerve DegenerationProtein AggregatesSirolimusTransgenesDNA-Binding ProteinsProtein AggregatesSirolimus

Identifiers

PMID34518579
PMCPMC8438029

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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.