ArticleActa neuropathologica communications2024
Dysregulation of stress granule dynamics by DCTN1 deficiency exacerbates TDP-43 pathology in Drosophila models of ALS/FTD.
Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- TSC2 is a stress granule suppressor.bioRxiv : the preprint server for biology · 2026Article
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Endozoicomonas acroporae enhances coral thermal resilience through host-microbe coordination.The ISME journal · 2026Article
- PolyQ-Expansion of Ataxin-2 Disrupts Microtubule Stability and Impairs Axon Outgrowth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- Cytoplasmic accumulation of a splice variant of hnRNPA2/B1 contributes to FUS-associated toxicity in a mouse model of ALS.Cell death & disease · 2025Article
- TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.Frontiers in cellular neuroscience · 2025Review
- A Novel De Novo Missense Mutation inInternational journal of molecular sciences · 2024Article
- Nanoplastics and Neurodegeneration in ALS.Brain sciences · 2024Review
- Dynactin-1 mediates rescue of impaired axonal transport due to reduced mitochondrial bioenergetics in amyotrophic lateral sclerosis motor neurons.Brain communications · 2024Article
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Authors and funding
15 authors at 6 institutions in 1 country.
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Abstract
The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo. We demonstrated using a Drosophila model of ALS/FTD that genetic knockdown of DCTN1 accelerates the formation of ubiquitin-positive cytoplasmic inclusions of TDP-43. Knockdown of components of other microtubule-associated motor protein complexes, including dynein and kinesin, also increased the formation of TDP-43 inclusions, indicating that intracellular transport along microtubules plays a key role in TDP-43 pathology. Notably, DCTN1 knockdown delayed the disassembly of stress granules in stressed cells, leading to an increase in the formation of pathological cytoplasmic inclusions of TDP-43. Our results indicate that a deficiency in DCTN1, as well as disruption of intracellular transport along microtubules, is a modifier that drives the formation of TDP-43 pathology through the dysregulation of stress granule dynamics.
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