Evidence map›Paper›PMID 41885937›Full record

ArticleJCI insight2026

KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS.

Tetsuya Akiyama, Yi Zeng, Caiwei Guo, Olivia Gautier, Lauren Koepke, Heankel Lyons, Elana Molotsky, Juliane S Bombosch, Odilia Sianto, Jay P Ross and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Tetsuya AkiyamaDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Yi ZengDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Caiwei GuoDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Olivia GautierDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Lauren KoepkeDepartment of Neurology and Neurological Sciences, and.
Heankel LyonsDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Elana MolotskyDepartment of Neurology and.
Juliane S BomboschDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Odilia SiantoDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Jay P RossDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Phuong HoangDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Luke ZhaoDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Cole SpencerDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.
Charlotte J SumnerDepartment of Neurology and.
Michelle MonjeDepartment of Neurology and Neurological Sciences, and.
John W DayDepartment of Neurology and Clinical Neurosciences, Stanford University, Stanford, California, USA.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, California, USA.

Funding

Human Biomarkers CoreU54NS123743 · NINDS · STANFORD UNIVERSITY · PI GITLER, AARON D. · 2021 to 2025
$8.2M
Translating Pathomechanisms into Treatment for Spinal Muscular AtrophiesR35NS122306 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Charlotte Jane Sumner · 2021 to 2026
$6.3M
Stanford Training Program in Aging ResearchT32AG047126 · NIA · STANFORD UNIVERSITY · PI VYJEYANTHI S PERIYAKOIL, TONY WYSS-CORAY · 2014 to 2026
$4.3M
Defining modifiers and mechanisms of RAN translationR01AG064690 · NIA · STANFORD UNIVERSITY · PI Aaron D. Gitler, JOSEPH D PUGLISI · 2024 to 2026
$2.3M
Innovating next generation technologies to define mechanisms of neurodegenerative disease and devise therapeutic strategiesR35NS137159 · NINDS · STANFORD UNIVERSITY · PI Aaron D. Gitler · 2025 to 2026
$2.3M
NIA NIH HHS R01 AG064690NIA NIH HHS T32 AG047126NINDS NIH HHS R35 NS122306NINDS NIH HHS R35 NS137159NINDS NIH HHS U54 NS123743
6 · The paper itself

Abstract

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN1) gene leading to decreased SMN protein levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. SMN deficiency resulted in downregulation of kinesin heavy chain isoform 5A (KIF5A) in human neurons and in a mouse model of SMA. SMN associated with KIF5A mRNA and contributed to its stability. Reduced SMN levels impaired axon regeneration, which was rescued by KIF5A overexpression. Because KIF5A has also been connected to ALS, these findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as an SMN-regulated factor. Our findings suggest that SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.

Indexed as

Amyotrophic Lateral SclerosisAxonsKinesinsMuscular Atrophy, SpinalNerve RegenerationSurvival of Motor Neuron 1 ProteinAnimalsDisease Models, AnimalDown-RegulationHumansMiceMotor NeuronsKIF5A protein, humanKinesinsSMN1 protein, humanSmn1 protein, mouseSurvival of Motor Neuron 1 ProteinGeneticsNeuromuscular diseaseNeuroscience

Identifiers

PMID41885937
PMCPMC13232735

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.