ArticleAutophagy2019
The ALS-FTD-linked gene product, C9orf72, regulates neuronal morphogenesis via autophagy.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis.NPJ systems biology and applications · 2025Pooled it
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- C9orf72 deficiency impairs the autophagic response to aggregated TDP-25 and exacerbates TDP-25-mediated neurodegeneration in vivo.Acta neuropathologica communications · 2025Article
- Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.Acta neuropathologica communications · 2024Article
- Article
- ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.Acta pharmaceutica Sinica. B · 2024Article
- Molecular hallmarks of ageing in amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2024Review
- Rab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Article
- Cdk5 phosphorylation-dependent C9orf72 degradation promotes neuronal death in Parkinson's disease models.CNS neuroscience & therapeutics · 2023Article
- C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy.Nature communications · 2023Article
- Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.Nature reviews. Genetics · 2023Review
- Loss and recovery of myocardial mitochondria in mice under different tail suspension time: Apoptosis and mitochondrial fission, fusion and autophagy.Experimental physiology · 2023Article
- Cell-autonomous immune dysfunction driven by disrupted autophagy inScience advances · 2023Article
- Propranolol reduces the accumulation of cytotoxic aggregates in C9orf72-ALS/FTDCurrent research in neurobiology · 2023Article
- Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.Frontiers in cellular neuroscience · 2023Review
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD.Acta neuropathologica · 2022Article
- The contribution of proteasomal impairment to autophagy activation by C9orf72 poly-GA aggregates.Cellular and molecular life sciences : CMLS · 2022Article
- Organization of the autophagy pathway in neurons.Current opinion in neurobiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in C9orf72 leading to hexanucleotide expansions are the most common genetic causes for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A phenotype resembling ALS and FTD is seen in transgenic mice overexpressing the hexanucleotide expansions, but is absent in C9orf72-deficient mice. Thus, the exact function of C9orf72 in neurons and how loss of C9orf72 may contribute to neuronal dysfunction remains to be clearly defined. Here, we showed that primary hippocampal neurons cultured from c9orf72 knockout mice have reduced dendritic arborization and spine density. Quantitative proteomic analysis identified C9orf72 as a component of the macroautophagy/autophagy initiation complex composed of ULK1-RB1CC1-ATG13-ATG101. The association was mediated through the direct interaction with ATG13 via the isoform-specific carboxyl-terminal DENN and dDENN domain of C9orf72. Furthermore, c9orf72 knockout neurons showed reduced LC3-II puncta accompanied by reduced ULK1 levels, suggesting that loss of C9orf72 impairs basal autophagy. Conversely, wild-type neurons treated with a ULK1 kinase inhibitor showed a dose-dependent reduction of dendritic arborization and spine density. Furthermore, expression of the long isoform of human C9orf72 that interacts with the ULK1 complex, but not the short isoform, rescues autophagy and the dendritic arborization phenotypes of c9orf72 knockout neurons. Taken together, our data suggests that C9orf72 has a cell-autonomous role in neuronal and dendritic morphogenesis through promotion of ULK1-mediated autophagy.
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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.