ArticleScientific reports2016
ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- The Roles of Alix and VPS4A in Autophagy and Endosomal Pathways and Their Relation to HBV Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Controlling Biogenesis and Engineering of Exosomes to Inhibit Growth and Promote Death in Glioblastoma Multiforme.Brain sciences · 2026Review
- The ESCRT-0 protein HRS regulates hepatocellular lipid droplet catabolism.bioRxiv : the preprint server for biology · 2025Article
- Neuronal Deletion ofBiomolecules · 2025Article
- Identifying links between cardiovascular disease and insomnia by modeling genes from a pleiotropic locus.Disease models & mechanisms · 2025Article
- ESCRT Machinery in HBV Life Cycle: Dual Roles in Autophagy and Membrane Dynamics for Viral Pathogenesis.Cells · 2025Review
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Transcriptome profiles of organ tissues from pigs experimentally infected with African swine fever virus in early phase of infection.Emerging microbes & infections · 2024Article
- Neuroinflammation in Age-Related Neurodegenerative Diseases: Role of Mitochondrial Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
- NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.Cellular and molecular life sciences : CMLS · 2024Article
- Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy.American journal of human genetics · 2024Article
- ER stress elicits non-canonical CASP8 (caspase 8) activation on autophagosomal membranes to induce apoptosis.Autophagy · 2024Article
- Review
- Analysis of the neuromuscular deficits caused by STAM1 deficiency.Current research in neurobiology · 2024Article
- Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson's disease-linked LRRK2 kinase.eLife · 2023Article
- Nuclear pore complex and nucleocytoplasmic transport disruption in neurodegeneration.FEBS letters · 2023Review
- Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.Antioxidants (Basel, Switzerland) · 2022Article
- Regulation ofMolecular biology of the cell · 2022Article
- Specific microRNAs for Modulation of Autophagy in Spinal Cord Injury.Brain sciences · 2022Review
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endosomal sorting required for transport (ESCRT) complexes orchestrate endo-lysosomal sorting of ubiquitinated proteins, multivesicular body formation and autophagic degradation. Defects in the ESCRT pathway have been implicated in many neurodegenerative diseases, but the underlying molecular mechanisms that link them to neurodegeneration remain unknown. In this study, we showed that forebrain-specific ablation of ESCRT-0/Hrs induced marked hippocampal neuronal cell loss accompanied by the accumulation of ubiquitinated proteins, including α-synuclein, TDP-43 and huntingtin as well as the autophagic substrate SQSTM1/p62. Consistent with this, silencing of Hrs in cultured cells not only led to α-synuclein and TDP-43 accumulation in addition to impaired autophagic flux but also suppressed cell viability through the induction of ER stress followed by the activation of JNK and RIPK1, a key regulator of necroptosis. Moreover, necrostatin-1, a specific inhibitor of RIPK1, and pan-caspase inhibitors partially reduced the neurotoxicity in the Hrs-silenced cells. Altogether, these findings suggest that the disruption of ESCRT-0/Hrs in the nervous system compromises autophagic/lysosomal degradation of neurodegenerative disease-related proteins, which thereby triggers ER stress-mediated apoptotic and necroptotic cell death.
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