ArticleCell reports2017
Post-transcriptional Inhibition of Hsc70-4/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- Structural-functional network decoupling in early stage amyotrophic lateral sclerosis reveals cell-type specific transcriptional signatures.BMC medicine · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- Article
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- Chaperone dysfunction in motor neuron disease: new insights from studies of the SMN complex.Genetics · 2025Review
- 25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction.Pflugers Archiv : European journal of physiology · 2025Article
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1Experimental neurology · 2025Article
- Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.Nature communications · 2024Article
- Pathogenic TDP-43 accelerates the generation of toxic exon1 HTT in Huntington's disease knock-in mice.Aging cell · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.Nature communications · 2024Article
- Chaperoning the chaperones: Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.bioRxiv : the preprint server for biology · 2024Article
- Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.iScience · 2024Article
- A missense mutation in theFrontiers in neuroscience · 2024Article
- Proteomic analysis of the SMN complex reveals conserved and etiologic connections to the proteostasis network.Frontiers in RNA research · 2024Article
- Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current Evidence and Potential use.CNS & neurological disorders drug targets · 2024Review
11 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
15 authors at 5 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a synaptopathy accompanied by the presence of cytoplasmic aggregates containing TDP-43, an RNA-binding protein linked to ∼97% of ALS cases. Using a Drosophila model of ALS, we show that TDP-43 overexpression (OE) in motor neurons results in decreased expression of the Hsc70-4 chaperone at the neuromuscular junction (NMJ). Mechanistically, mutant TDP-43 sequesters hsc70-4 mRNA and impairs its translation. Expression of the Hsc70-4 ortholog, HSPA8, is also reduced in primary motor neurons and NMJs of mice expressing mutant TDP-43. Electrophysiology, imaging, and genetic interaction experiments reveal TDP-43-dependent defects in synaptic vesicle endocytosis. These deficits can be partially restored by OE of Hsc70-4, cysteine-string protein (Csp), or dynamin. This suggests that TDP-43 toxicity results in part from impaired activity of the synaptic CSP/Hsc70 chaperone complex impacting dynamin function. Finally, Hsc70-4/HSPA8 expression is also post-transcriptionally reduced in fly and human induced pluripotent stem cell (iPSC) C9orf72 models, suggesting a common disease pathomechanism.
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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.