Evidence map›Paper›PMID 42538636›Full record

ArticleAnnals of neurology2026

Establishing Sensory Neurons as Therapeutic Targets in Peripheral Neuropathy Driven by Polyglutamine Expanded Murine ATXN3.

Juan P Mato, John M Hayes, Jacen Emerson, Maeha Sridharan, Toluwani Adelaja, Arsal Naeem, Alexandra F Putka, Hayley S McLoughlin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Juan P MatoDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
John M HayesDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Jacen EmersonDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.ORCID https://orcid.org/0009-0007-6432-5057
Maeha SridharanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Toluwani AdelajaDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Arsal NaeemDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Alexandra F PutkaDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.ORCID https://orcid.org/0000-0003-3111-3465
Hayley S McLoughlinDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.ORCID https://orcid.org/0000-0003-4279-2758

Funding

Nonneuronal Mechanisms of Polyglutamine NeurodegenerationR01NS122751 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MCLOUGHLIN, HAYLEY S · 2021 to 2025
$2.2M
Investigating Peripheral Neuropathy in Spinocerebellar Ataxia Type 3R01NS140063 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Hayley S McLoughlin · 2025 to 2026
$944k
NINDS NIH HHS R01 NS122751NINDS NIH HHS R01 NS140063
6 · The paper itself

Abstract

objectiveRepeat expansion mutations underlie diverse neurogenetic disorders, many involving the peripheral nervous system. Despite peripheral neuropathy being the most common neurological disorder worldwide, its contribution to repeat expansion diseases remains poorly defined, and robust preclinical models are limited. We established a translational framework to study peripheral neuropathy in spinocerebellar ataxia type 3 (SCA3), a fatal multisystem disorder caused by a pathogenic CAG expansion in ATXN3.

methodsSCA3 Knock-In Atxn3

resultsKI mice developed progressive sensorimotor deficits, peripheral histopathology, and RNA splicing dysregulation that parallel clinical features of SCA3. In contrast, KO mice showed normal peripheral nerve function, implicating toxic gain-of-function from mutant ATXN3 as the causative driver. Sensory neuron-specific silencing of mutant ATXN3 significantly ameliorated peripheral nerve abnormalities and DRG splicing dysregulation.

interpretationThese findings define a pathogenic role for repeat expansion-driven peripheral nerve degeneration in SCA3, identify sensory neurons as key therapeutic targets, and provide a preclinical platform for developing peripheral interventions in SCA3 and related repeat expansion disorders. ANN NEUROL 2026;100:1039-1054.

Indexed as

Ataxin-3Machado-Joseph DiseasePeptidesPeripheral Nervous System DiseasesSensory Receptor CellsAnimalsDisease Models, AnimalGanglia, SpinalMaleMiceMice, KnockoutMice, TransgenicTrinucleotide Repeat ExpansionAtaxin-3Atxn3 protein, mousePeptidespolyglutamine

Identifiers

PMID42538636
PMCPMC13688050

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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.