ArticleBrain : a journal of neurology2023
Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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.
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.
Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis.Scientific reports · 2026Article
- The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention.Frontiers in molecular neuroscience · 2026Review
- Unravelling the myriad physiologic roles of transthyretin: critical considerations for treating transthyretin amyloidosis.Annals of medicine · 2025Review
- Transthyretin abnormalities in amyotrophic lateral sclerosis: High molecular weight species in cerebrospinal fluid and stromal deposits in choroid plexus.Journal of neuropathology and experimental neurology · 2025Article
- Inborn errors of canonical autophagy in neurodegenerative diseases.Human molecular genetics · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2024Article
- The pathogenic mechanism of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis.Neural regeneration research · 2024Review
- TTR (transthyretin) leads the autophagy disaster relief team against TARDBP/TDP-43 proteinopathy.Autophagy · 2023Article
- Early activation of cellular stress and death pathways caused by cytoplasmic TDP-43 in the rNLS8 mouse model of ALS and FTD.Molecular psychiatry · 2023Article
- Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations.Brain communications · 2023Review
Corrections and comments
- Commented on by
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.
Indexed as
Identifiers
What OpenQuestion holds
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.