ArticleNeuroscience bulletin2020
Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS.
Article in Neuroscience bulletin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Decoding Nucleotide Repeat Expansion Diseases: Novel Insights fromInternational journal of molecular sciences · 2024Review
- A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD.Molecules and cells · 2024Article
- The Effect of theInternational journal of molecular sciences · 2023Article
- UNC13A Gene Brings New Hope for ALS Disease-Modifying Drugs.Neuroscience bulletin · 2022Article
- The noncanonical role of the protease cathepsin D as a cofilin phosphatase.Cell research · 2021Article
- Degeneration Versus Development: Hunting-Out the D-Unit of Huntington's Disease.Neuroscience bulletin · 2021Article
- Tau Accumulation and Defective Autophagy: A Common Pathological Mechanism Underlying Repeat-Expansion-Induced Neurodegenerative Diseases?Neuroscience bulletin · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome-lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.
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