ArticleCurrent biology : CB2017
Stall in Canonical Autophagy-Lysosome Pathways Prompts Nucleophagy-Based Nuclear Breakdown in Neurodegeneration.
Article in Current biology : CB, 2017. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Selective autophagy of intracellular organelles: recent research advances.Theranostics · 2021Pooled it
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Longitudinal Transcriptomic Analysis Reveals Systemic Effects of Risdiplam in Adults with Spinal Muscular Atrophy.Brain sciences · 2026Article
- Pathogenic variants in the autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation.Nature communications · 2026Article
- Autophagy Dysfunction and Neurodegeneration: Where Does It Go Wrong?Journal of molecular biology · 2025Review
- Autophagy is an upstream mediator of chromatin dynamics in normal and autoimmune germinal center B cells.The Journal of clinical investigation · 2025Article
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Organellophagy regulates cell death:A potential therapeutic target for inflammatory diseases.Journal of advanced research · 2025Review
- Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissues.Brain : a journal of neurology · 2025Article
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Genetic modeling of degenerative diseases and mechanisms of neuronal regeneration in the zebrafish cerebellum.Cellular and molecular life sciences : CMLS · 2024Review
- Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle.Nucleus (Austin, Tex.) · 2024Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Nuclear poly-glutamine aggregates rupture the nuclear envelope and hinder its repair.The Journal of cell biology · 2024Article
- Human TDP43 is required for ALS‑related annexin A11 toxicity inBiomedical reports · 2024Article
- GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons.CNS neuroscience & therapeutics · 2024Article
- 20- Deoxyingenol attenuate morphine-induced hippocampus neurotoxicity and memory impairments in rats.Heliyon · 2024Article
- The impact of VPS35 D620N mutation on alternative autophagy and its reversal by estrogen in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Article
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12 authors at 4 institutions in 2 countries.
Funding
Abstract
The terminal stages of neuronal degeneration and death in neurodegenerative diseases remain elusive. Autophagy is an essential catabolic process frequently failing in neurodegeneration. Selective autophagy routes have recently emerged, including nucleophagy, defined as degradation of nuclear components by autophagy. Here, we show that, in a mouse model for the polyglutamine disease dentatorubral-pallidoluysian atrophy (DRPLA), progressive acquirement of an ataxic phenotype is linked to severe cerebellar cellular pathology, characterized by nuclear degeneration through nucleophagy-based LaminB1 degradation and excretion. We find that canonical autophagy is stalled in DRPLA mice and in human fibroblasts from patients of DRPLA. This is evidenced by accumulation of p62 and downregulation of LC3-I/II conversion as well as reduced Tfeb expression. Chronic autophagy blockage in several conditions, including DRPLA and Vici syndrome, an early-onset autolysosomal pathology, leads to the activation of alternative clearance pathways including Golgi membrane-associated and nucleophagy-based LaminB1 degradation and excretion. The combination of these alternative pathways and canonical autophagy blockade, results in dramatic nuclear pathology with disruption of the nuclear organization, bringing about terminal cell atrophy and degeneration. Thus, our findings identify a novel progressive mechanism for the terminal phases of neuronal cell degeneration and death in human neurodegenerative diseases and provide a link between autophagy block, activation of alternative pathways for degradation, and excretion of cellular components.
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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.