ArticleScientific reports2022
Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The Clinicopathological Significance of BiP/GRP-78 in Breast Cancer: A Meta-Analysis of Public Datasets and Immunohistochemical Detection.Current oncology (Toronto, Ont.) · 2022Pooled it
- Network Biology of Alzheimer's Disease and Related Neurodegenerative Disorders: Molecular Mechanisms and Therapeutic Strategies.Biomolecules · 2026Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Dark and camouflaged genomic regions remain challenging in CHM13.Scientific reports · 2026Article
- GRP78 in human diseases: From molecular chaperone to therapeutic target.Theranostics · 2026Review
- Expression and role of HSPA5 in environmental toxin-induced neurological disorders.Frontiers in molecular neuroscience · 2026Review
- Aberrant NSUN1 activity connects mLife science alliance · 2026Article
- Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular-Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report.Diseases (Basel, Switzerland) · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Large-scale purifications reveal yeast and human stress granule cores are heterogeneous particles with complex transcriptomes and proteomes.Cell reports · 2025Article
- Caloric restriction mimetic 2-deoxyglucose alters metabolic and transcriptomic phenotype in association with changes in chromatin accessibility in human astrocytes.Scientific reports · 2025Article
- Sequencing the gaps: dark genomic regions persist in CHM13 despite long-read advances.bioRxiv : the preprint server for biology · 2025Article
- Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.bioRxiv : the preprint server for biology · 2025Article
- Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.bioRxiv : the preprint server for biology · 2025Article
- Werner syndrome exonuclease promotes gut regeneration and causes age-associated gut hyperplasia in Drosophila.PLoS biology · 2025Article
- Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease.Neurobiology of disease · 2025Article
- Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease.Cells · 2025Review
- Article
- RNA binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs.Biophysical journal · 2024Article
- TDP-43 in nuclear condensates: where, how, and why.Biochemical Society transactions · 2024Review
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Authors and funding
16 authors at 8 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure or effective treatment in which TAR DNA Binding Protein of 43 kDa (TDP-43) abnormally accumulates into misfolded protein aggregates in affected neurons. It is widely accepted that protein misfolding and aggregation promotes proteotoxic stress. The molecular chaperones are a primary line of defense against proteotoxic stress, and there has been long-standing interest in understanding the relationship between chaperones and aggregated protein in ALS. Of particular interest are the heat shock protein of 70 kDa (Hsp70) family of chaperones. However, defining which of the 13 human Hsp70 isoforms is critical for ALS has presented many challenges. To gain insight into the specific Hsp70 that modulates TDP-43, we investigated the relationship between TDP-43 and the Hsp70s using proximity-dependent biotin identification (BioID) and discovered several Hsp70 isoforms associated with TDP-43 in the nucleus, raising the possibility of an interaction with native TDP-43. We further found that HspA5 bound specifically to the RNA-binding domain of TDP-43 using recombinantly expressed proteins. Moreover, in a Drosophila strain that mimics ALS upon TDP-43 expression, the mRNA levels of the HspA5 homologue (Hsc70.3) were significantly increased. Similarly we observed upregulation of HspA5 in prefrontal cortex neurons from human ALS patients. Finally, overexpression of HspA5 in Drosophila rescued TDP-43-induced toxicity, suggesting that upregulation of HspA5 may have a compensatory role in ALS pathobiology.
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