ArticleThe Journal of cell biology2021
TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 50 citations in OpenAlex.
- Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.Trends in cell biology · 2026Review
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Deletion ofBiology · 2026Article
- Shared genetic link and causal inference between blood lipids, lipid-lowering drugs and amyotrophic lateral sclerosis.Neural regeneration research · 2026Article
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- Regulation of Neuronal Senescence byBiology · 2026Article
- Subtype-specific associations between serum lipid profiles and disease severity in patients with amyotrophic lateral sclerosis.Biomedical reports · 2026Article
- Hmgcs1 regulates cholesterol synthesis and promotes nerve fiber repair after spinal cord injury.iScience · 2026Article
- Lisinopril activates BI1 to reprogram lipid metabolism and restore autophagy in ALS.Communications biology · 2026Article
- Intraoperative Lipoproteins Associated with Postoperative Delirium in a Prospective Observational Study of Older Adults Undergoing Cardiac Surgery.Journal of cardiothoracic and vascular anesthesia · 2026Observational
- Article
- Role of LXRβ in oligodendrocytes in neuronal survival.Molecular psychiatry · 2026Article
- Article
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.Research square · 2025Article
- TDP-43: unveiling the hidden key to cellular fate decisions.Cell communication and signaling : CCS · 2025Review
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.bioRxiv : the preprint server for biology · 2025Article
- TDP-43 dysregulation impairs cholesterol metabolism linked with myelination defects.Acta neuropathologica · 2025Article
- Methylome analysis of FTLD patients with TDP-43 pathology identifies epigenetic signatures specific to pathological subtypes.Molecular neurodegeneration · 2025Article
- Fluorescence Lifetime-Based FRET Biosensors for Monitoring N Terminal Domain-Dependent Interactions of TDP-43 in Living Cells: A Novel Approach for ALS and FTD Drug Discovery.ACS chemical neuroscience · 2025Article
- Alterations of Fat and Ketone Body Metabolism in ALS and SMA-A Prospective Observational Study.European journal of neurology · 2025Observational
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Cholesterol metabolism operates autonomously within the central nervous system (CNS), where the majority of cholesterol resides in myelin. We demonstrate that TDP-43, the pathological signature protein for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), influences cholesterol metabolism in oligodendrocytes. TDP-43 binds directly to mRNA of SREBF2, the master transcription regulator for cholesterol metabolism, and multiple mRNAs encoding proteins responsible for cholesterol biosynthesis and uptake, including HMGCR, HMGCS1, and LDLR. TDP-43 depletion leads to reduced SREBF2 and LDLR expression, and cholesterol levels in vitro and in vivo. TDP-43-mediated changes in cholesterol levels can be restored by reintroducing SREBF2 or LDLR. Additionally, cholesterol supplementation rescues demyelination caused by TDP-43 deletion. Furthermore, oligodendrocytes harboring TDP-43 pathology from FTD patients show reduced HMGCR and HMGCS1, and coaggregation of LDLR and TDP-43. Collectively, our results indicate that TDP-43 plays a role in cholesterol homeostasis in oligodendrocytes, and cholesterol dysmetabolism may be implicated in TDP-43 proteinopathies-related diseases.
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Registered trials
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.