ArticleNeuron2023
Downregulation of Hsp90 and the antimicrobial peptide Mtk suppresses poly(GR)-induced neurotoxicity in C9ORF72-ALS/FTD.
Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Hyperoside protects against poly-GR-mediated neurodegeneration via regulation of mitochondrial fission and oxidative stress in C9orf72-associated ALS.Chinese medicine · 2026Article
- Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.Frontiers in aging neuroscience · 2026Review
- Immune crosstalk in Alzheimer's and Parkinson's disease: insights from Drosophila models into the brain-peripheral immune axis.Frontiers in immunology · 2026Review
- The Ku80-p53-SIRT1 axis in DNA damage response contributes to sporadic and familial ALS and FTD.Nature communications · 2025Article
- Revealing the molecular mechanisms of levofloxacin-induced cognitive impairment and epilepsy: an integrated bioinformatics and molecular dynamics simulation.BMC pharmacology & toxicology · 2025Article
- High-rate mechano-stimulation alters proliferation- and maturation-related signaling of oligodendrocyte precursor cells in a 3D hydrogel.Mechanobiology in medicine · 2025Article
- Glucose uptake in pigment glia suppresses Tau-induced inflammation and photoreceptor degeneration.Disease models & mechanisms · 2025Article
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.Life science alliance · 2025Article
- Non-Immune Functions of Innate Immunity Acting on Physiological Processes: Insights fromInternational journal of molecular sciences · 2025Review
- Decoding Nucleotide Repeat Expansion Diseases: Novel Insights fromInternational journal of molecular sciences · 2024Review
- Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration.Trends in neurosciences · 2024Review
- The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.Cell reports · 2024Article
- Article
- A single amino acid polymorphism in natural Metchnikowin alleles of Drosophila results in systemic immunity and life history tradeoffs.PLoS genetics · 2024Article
- Closest horizons of Hsp70 engagement to manage neurodegeneration.Frontiers in molecular neuroscience · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
GGGGCC repeat expansion in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat RNAs can be translated into dipeptide repeat proteins, including poly(GR), whose mechanisms of action remain largely unknown. In an RNA-seq analysis of poly(GR) toxicity in Drosophila, we found that several antimicrobial peptide genes, such as metchnikowin (Mtk), and heat shock protein (Hsp) genes are activated. Mtk knockdown in the fly eye or in all neurons suppresses poly(GR) neurotoxicity. These findings suggest a cell-autonomous role of Mtk in neurodegeneration. Hsp90 knockdown partially rescues both poly(GR) toxicity in flies and neurodegeneration in C9ORF72 motor neurons derived from induced pluripotent stem cells (iPSCs). Topoisomerase II (TopoII) regulates poly(GR)-induced upregulation of Hsp90 and Mtk. TopoII knockdown also suppresses poly(GR) toxicity in Drosophila and improves survival of C9ORF72 iPSC-derived motor neurons. These results suggest potential novel therapeutic targets for C9ORF72-ALS/FTD.
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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.