Evidence map›Paper›PMID 42051315›Full record

ArticlebioRxiv : the preprint server for biology2026

Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.

Matthew Nolan, Sandeep Aryal, I Sandra Ndayambaje, Maize Cao, Peyton Lee, Moriah Hovde, Shuqi Yun, Josette Wlaschin, Aaron Held, Hortense Beaussant and 31 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

41 authors.

Matthew NolanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sandeep AryalDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
I Sandra NdayambajeDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Maize CaoDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Peyton LeeEunice Kennedy Shriver National Institute for Child Health and Development, Bethesda, Maryland, USA.
Moriah HovdeDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shuqi YunCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Josette WlaschinEunice Kennedy Shriver National Institute for Child Health and Development, Bethesda, Maryland, USA.
Aaron HeldDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Hortense BeaussantDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Benjamin WymannDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Chao Zong-LeeDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Su Min LimDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Xin JiangDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nandini RameshDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ana Rita Agra Almeida QuadrosDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ayub BoulosDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nicolas ZinterDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shireen SalemDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Laïla El-TayarDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Melinda BeccariDepartment of Cellular and Molecular Medicine, University of California, San Diego, USA.
Maximiliano PresaThe Jackson Laboratory, Bar Harbor, ME, USA.
Charles Jourdan Ferreras ReyesDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Yin Yin RuanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Grant GriesmanDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Corey AguilarDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
James HawrotNational Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Hayden WheelerDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Zevik MelamedDepartment of Cellular and Molecular Medicine, University of California, San Diego, USA.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Mark AlbersDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Don W ClevelandDepartment of Cellular and Molecular Medicine, University of California, San Diego, USA.
Rudolph E TanziDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cathleen M LutzThe Jackson Laboratory, Bar Harbor, ME, USA.
Robert D HubbardMass General Brigham Innovation, Mass General Brigham, Boston, USA.
Dione KobayashiMass General Brigham Innovation, Mass General Brigham, Boston, USA.
Michael WardNational Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Christiano R R AlvesDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Brian WaingerDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Claire Le PichonEunice Kennedy Shriver National Institute for Child Health and Development, Bethesda, Maryland, USA.
Clotilde Lagier-TourenneDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Funding

The neuronal stress response in neurodegenerative disease and painZIAHD008966 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LE PICHON, CLAIRE · 2017 to 2025
$17.1M
Targeting Dysregulated RNA Splicing in Neurodegenerative DiseasesRM1NS133601 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Clotilde Lagier-Tourenne, Michael Emmerson Ward · 2023 to 2026
$7.4M
Determining stathmin-2 function and potential as a therapeutic target in ALS/FTDR01NS112503 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CLEVELAND, DON W, LAGIER-TOURENNE, CLOTILDE · 2020 to 2024
$4.1M
In vivo modelling and therapy development for stathmin-2 loss in TDP-43 proteinopathiesRF1NS124203 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CLEVELAND, DON W, LAGIER-TOURENNE, CLOTILDE · 2021 to 2021
$2.5M
Scalable Development of Custom Genome Editing TechnologiesDP2CA281401 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2022 to 2025
$2.5M
Multidisciplinary training in basic and translational Alzheimer's disease researchT32AG066596 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 2020 to 2024
$2.2M
Development of in Vivo Base Editing as a Genetic Treatment for Spinal Muscular AtrophyK01NS134784 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Christiano Alves · 2024 to 2026
$726k
Intramural NIH HHS ZIA HD008966NCI NIH HHS DP2 CA281401NIA NIH HHS T32 AG066596NINDS NIH HHS K01 NS134784NINDS NIH HHS R01 NS112503NINDS NIH HHS RF1 NS124203NINDS NIH HHS RM1 NS133601
6 · The paper itself

Abstract

Loss of neuronal regenerative capacity is a common feature of neurodegenerative disease and axonal injury, yet the transcriptional programs governing this state remain poorly defined. Stathmin-2 (STMN2), a tubulin-binding protein essential for axon maintenance and repair, is profoundly depleted following loss of nuclear TDP-43 in neurodegenerative disease. Here, we identify statins as potent inducers of STMN2 expression. Pharmacological and genetic suppression of the mevalonate pathway, and subsequent prevention of protein geranylgeranylation, restored STMN2 levels in TDP-43 deficient cells and promoted neurite growth. STMN2 induction was abrogated when using a statin analogue unable to interact with HMG-CoA reductase, and through co-administration of mevalonate or geranylgeranyl diphosphate substrates. RNA-seq revealed that statins induce a coordinated pro-regenerative transcriptional response, including activation of the AP-1 transcription factor complex gene,

Indexed as

Amyotrophic lateral sclerosisATF3axonFrontotemporal dementiamevalonate pathwayneurodegenerative diseasesprenylationstatinSTMN2TARDBPTDP-43

Identifiers

PMID42051315
PMCPMC13119319

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.