ArticleThe Journal of biological chemistry2009
Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03359538 (Rapamycin), which is not on this map. Cited by 96 papers.
What it found
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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.
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.
Rapamycin (Sirolimus) Treatment for Amyotrophic Lateral Sclerosis
Who cites it
96 citing papers in PubMed, 166 citations in OpenAlex.
- Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.Nature communications · 2023Trial
- Trial
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- Protease-Mediated TAR DNA-Binding Protein 43 (TDP-43) Pathogenesis: From Molecular Mechanisms to Therapeutic Opportunities.ACS pharmacology & translational science · 2026Review
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment.CNS & neurological disorders drug targets · 2026Review
- Article
- A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.The FEBS journal · 2025Article
- The Role of mTOR in Amyotrophic Lateral Sclerosis.Biomedicines · 2025Review
- Targeting common disease pathomechanisms to treat amyotrophic lateral sclerosis.Nature reviews. Neurology · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Combined Treatment with Bojungikgi-tang (Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells.Chinese journal of integrative medicine · 2024Article
- The endolysosomal pathway and ALS/FTD.Trends in neurosciences · 2023Review
- From Recognition to Remedy: The Significance of Biomarkers in Neurodegenerative Disease Pathology.International journal of molecular sciences · 2023Review
- Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?Antioxidants (Basel, Switzerland) · 2023Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TDP-43 is a nuclear protein involved in exon skipping and alternative splicing. Recently, TDP-43 has been identified as the pathological signature protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. In addition, TDP-43-positive inclusions are present in Parkinson disease, dementia with Lewy bodies, and 30% of Alzheimer disease cases. Pathological TDP-43 is redistributed from the nucleus to the cytoplasm, where it accumulates. An approximately 25-kDa C-terminal fragment of TDP-43 accumulates in affected brain regions, suggesting that it may be involved in the disease pathogenesis. Here, we show that overexpression of the 25-kDa C-terminal fragment is sufficient to cause the mislocalization and cytoplasmic accumulation of endogenous full-length TDP-43 in two different cell lines, thus recapitulating a key biochemical characteristic of TDP-43 proteinopathies. We also found that TDP-43 mislocalization is associated with a reduction in the low molecular mass neurofilament mRNA levels. Notably, we show that the autophagic system plays a role in TDP-43 metabolism. Specifically, we found that autophagy inhibition increases the accumulation of the C-terminal fragments of TDP-43, whereas inhibition of mTOR, a key protein kinase involved in autophagy regulation, reduces the 25-kDa C-terminal fragment accumulation and restores TDP-43 localization. Our results suggest that autophagy induction may be a valid therapeutic target for TDP-43 proteinopathies.
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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.