ArticleActa neuropathologica communications2018
Dipeptide repeat proteins activate a heat shock response found in C9ORF72-ALS/FTLD patients.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity.bioRxiv : the preprint server for biology · 2024Article
- Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.Nature aging · 2024Article
- Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia.Acta neuropathologica · 2024Article
- Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.Frontiers in molecular neuroscience · 2024Review
- Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues.Cell reports · 2023Article
- Review
- Proximity proteomics of C9orf72 dipeptide repeat proteins identifies molecular chaperones as modifiers of poly-GA aggregation.Acta neuropathologica communications · 2022Article
- CRISPR deletion of the C9ORF72 promoter in ALS/FTD patient motor neurons abolishes production of dipeptide repeat proteins and rescues neurodegeneration.Acta neuropathologica · 2020Article
- Knocking out C9ORF72 Exacerbates Axonal Trafficking Defects Associated with Hexanucleotide Repeat Expansion and Reduces Levels of Heat Shock Proteins.Stem cell reports · 2020Article
- Glial Cells-The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment.Journal of clinical medicine · 2020Review
- BV-2 Microglial Cells OverexpressingFrontiers in neurology · 2020Article
- Production of poly(GA) in C9ORF72 patient motor neurons derived from induced pluripotent stem cells.Acta neuropathologica · 2019Article
- Transcription elongation factor AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD.Nature communications · 2019Article
- Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD.Nature neuroscience · 2019Article
- Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies.Acta neuropathologica communications · 2019Article
- eIF4B and eIF4H mediate GR production from expanded G4C2 in a Drosophila model for C9orf72-associated ALS.Acta neuropathologica communications · 2019Article
- Heterochromatin anomalies and double-stranded RNA accumulation underlieScience (New York, N.Y.) · 2019Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
A hexanucleotide (GGGGCC) repeat expansion in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Reduced expression of the C9ORF72 gene product has been proposed as a potential contributor to disease pathogenesis. Additionally, repetitive RNAs and dipeptide repeat proteins (DPRs), such as poly-GR, can be produced by this hexanucleotide expansion that disrupt a number of cellular processes, potentially contributing to neural degeneration. To better discern which of these mechanisms leads to disease-associated changes in patient brains, we analyzed gene expression data generated from the cortex and cerebellum. We found that transcripts encoding heat shock proteins (HSPs) regulated by the HSF1 transcription factor were significantly induced in C9ORF72-ALS/FTLD patients relative to both sporadic ALS/FTLD cases and controls. Treatment of human neurons with chemically synthesized DPRs was sufficient to activate a similar transcriptional response. Expression of GGGGCC repeats and also poly-GR in the brains of Drosophila lead to the upregulation of HSF1 and the same highly-conserved HSPs. Additionally, HSF1 was a modifier of poly-GR toxicity in Drosophila. Our results suggest that the expression of DPRs are associated with upregulation of HSF1 and activation of a heat shock response in C9ORF72-ALS/FTLD.
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