ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2015
TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 208 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
208 citing papers in PubMed, 3 syntheses or guidelines pooled it, 348 citations in OpenAlex.
- The contribution of brain banks to knowledge discovery in amyotrophic lateral sclerosis: A systematic review.Neuropathology and applied neurobiology · 2022Pooled it
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis.Neuropathology and applied neurobiology · 2018Pooled it
- Neutralization of pathogenic PC-OxPL by AAV-delivered scFv as a therapeutic strategy for amyotrophic lateral sclerosis.Molecular therapy. Advances · 2026Article
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- Nanoscale morphological and structural analysis of round and donut oligomers formed by C-terminal domain of TDP-43.Physical chemistry chemical physics : PCCP · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis.Annals of neurology · 2026Article
- Poncirin Alleviates Hypoxic Pulmonary Hypertension by Blocking TDP43-Mediated Macrophage Pyroptosis.Pulmonary circulation · 2026Article
- The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.International journal of molecular sciences · 2026Review
- Polymeric lysosome-targeting chimeras for extracellular α-synuclein degradation in Parkinson's disease.Acta neuropathologica communications · 2026Review
- Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case-control study.IBRO neuroscience reports · 2026Article
- Subtype-specific associations between serum lipid profiles and disease severity in patients with amyotrophic lateral sclerosis.Biomedical reports · 2026Article
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- Stability and Dynamics of the N‑Terminal Domain of TDP-43 and the Effect of Point Mutations.ACS omega · 2026Article
- TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis.Acta neuropathologica · 2026Article
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibrils.ACS chemical neuroscience · 2026Article
- Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
148 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Therapeutic options for patients with amyotrophic lateral sclerosis (ALS) are currently limited. However, recent studies show that almost all cases of ALS, as well as tau-negative frontotemporal dementia (FTD), share a common neuropathology characterized by the deposition of TAR-DNA binding protein (TDP)-43-positive protein inclusions, offering an attractive target for the design and testing of novel therapeutics. Here we demonstrate how diverse environmental stressors linked to stress granule formation, as well as mutations in genes encoding RNA processing proteins and protein degradation adaptors, initiate ALS pathogenesis via TDP-43. We review the progressive development of TDP-43 proteinopathy from cytoplasmic mislocalization and misfolding through to macroaggregation and the addition of phosphate and ubiquitin moieties. Drawing from cellular and animal studies, we explore the feasibility of therapeutics that act at each point in pathogenesis, from mitigating genetic risk using antisense oligonucleotides to modulating TDP-43 proteinopathy itself using small molecule activators of autophagy, the ubiquitin-proteasome system, or the chaperone network. We present the case that preventing the misfolding of TDP-43 and/or enhancing its clearance represents the most important target for effectively treating ALS and frontotemporal dementia.
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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.