Evidence map›Paper›PMID 24908668›Full record

ArticleHuman molecular genetics2014

Pharmacologic rescue of axon growth defects in a human iPSC model of hereditary spastic paraplegia SPG3A.

Peng-Peng Zhu, Kyle R Denton, Tyler Mark Pierson, Xue-Jun Li, Craig Blackstone

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

Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.5field-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

45 citing papers in PubMed, 67 citations in OpenAlex.

  1. ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER-Mitochondria Contact Sites.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  14. Hereditary Spastic Paraplegia: An Update.International journal of molecular sciences · 2022
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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 4 institutions in 1 country.

Peng-Peng ZhuNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Kyle R DentonDepartment of Neuroscience and.
Tyler Mark PiersonDepartments of Pediatrics and Neurology and the Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Xue-Jun LiDepartment of Neuroscience and The Stem Cell Institute, University of Connecticut Health Center, Farmington, CT 06030, USA and xjli@uchc.edu.
Craig BlackstoneNeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Cedars-Sinai Medical Center · USNational Institute of Neurological Disorders and Stroke · USNational Institutes of Health · USUConn Health · US

Funding

Molecular Pathogenesis Of Hereditary Spastic ParaplegiasZIANS002992 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BLACKSTONE, CRAIG · 2009 to 2021
$20.6M
Intramural NIH HHS
6 · The paper itself

Abstract

Hereditary spastic paraplegias are a large, diverse group of neurological disorders (SPG1-71) with the unifying feature of prominent lower extremity spasticity, owing to a length-dependent axonopathy of corticospinal motor neurons. The most common early-onset form of pure, autosomal dominant hereditary spastic paraplegia is caused by mutation in the ATL1 gene encoding the atlastin-1 GTPase, which mediates homotypic fusion of ER tubules to form the polygonal ER network. We have identified a p.Pro342Ser mutation in a young girl with pure SPG3A. This residue is in a critical hinge region of atlastin-1 between its GTPase and assembly domains, and it is conserved in all known eukaryotic atlastin orthologs. We produced induced pluripotent stem cells from skin fibroblasts and differentiated these into forebrain neurons to generate a human neuronal model for SPG3A. Axons of these SPG3A neurons showed impaired growth, recapitulating axonal defects in atlastin-1-depleted rat cortical neurons and impaired root hair growth in loss-of-function mutants of the ATL1 ortholog rhd3 in the plant Arabidopsis. Both the microtubule cytoskeleton and tubular ER are important for mitochondrial distribution and function within cells, and SPG3A neurons showed alterations in mitochondrial motility. Even so, it is not clear whether this change is involved in disease pathogenesis. The SPG3A axon growth defects could be rescued with microtubule-binding agents, emphasizing the importance of tubular ER interactions with the microtubule cytoskeleton in hereditary spastic paraplegia pathogenesis. The prominent alterations in axon growth in SPG3A neurons may represent a particularly attractive target for suppression in screens for novel pharmacologic agents.

Indexed as

Amino Acid SequenceAnimalsAxonsCell DifferentiationCell LineChild, PreschoolDNA Mutational AnalysisFemaleGTP-Binding ProteinsHeterozygoteHumansInduced Pluripotent Stem CellsMembrane ProteinsModels, MolecularMolecular Sequence DataMutationATL1 protein, humanGTP-Binding ProteinsMembrane ProteinsTubulin Modulators

Identifiers

PMID24908668
PMCPMC4189900
OpenAlexW2160641644

What OpenQuestion holds

Textmetadata
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.