ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
S-Nitrosylation of p62 Inhibits Autophagic Flux to Promote α-Synuclein Secretion and Spread in Parkinson's Disease and Lewy Body Dementia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 50 citations in OpenAlex.
- Nitric oxide signaling and mitophagy in Parkinson's disease: implications for aerobic exercise-related neuroprotection.Medical gas research · 2027Review
- Review
- Homocysteine and mitophagy in diabetic retinopathy: unraveling the underlying molecular crosstalk.Endocrine · 2026Review
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Nitric Oxide-Mediated S-Nitrosylation of TSC2 Drives mTOR dysregulation across Shank3 and Cntnap2 Models of Autism Spectrum Disorder.Molecular psychiatry · 2026Article
- CRISPR-Based Gene Therapy for Brain Disease.Molecular neurobiology · 2026Review
- Molecular and Structural Characterization Reveals Divergent Extracellular Vesicle Profiles Between Wild Type and Alzheimer's Disease Cerebrocortical Organoids.bioRxiv : the preprint server for biology · 2026Article
- Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.Journal of neurochemistry · 2026Review
- Targeting neuroinflammation in neurodegenerative disorders: the emerging potential of semaglutide.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- SQSTM1/p62 UFMylation Enhances Autophagic Clearance of Pathogenic Mutant Huntingtin.International journal of biological sciences · 2026Article
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- The role of energy deficit in autophagy failure in Parkinson's disease.Frontiers in aging neuroscience · 2026Review
- Nitric oxide: a gas transmitter in healthy and diseased skin.Medical gas research · 2025Review
- Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Aberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Multi-omics study reveals differential expression and phosphorylation of autophagy-related proteins in autism spectrum disorder.Scientific reports · 2025Article
- Canonical and noncanonical autophagy: involvement in Parkinson's disease.Frontiers in cell and developmental biology · 2025Review
- Proteomic signatures of Alzheimer's disease and Lewy body dementias: A comparative analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.Autophagy reports · 2025Review
- Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer's and related dementias.Neuron · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of autophagic pathways leads to accumulation of abnormal proteins and damaged organelles in many neurodegenerative disorders, including Parkinson's disease (PD) and Lewy body dementia (LBD). Autophagy-related dysfunction may also trigger secretion and spread of misfolded proteins, such as α-synuclein (α-syn), the major misfolded protein found in PD/LBD. However, the mechanism underlying these phenomena remains largely unknown. Here, we used cell-based models, including human induced pluripotent stem cell-derived neurons, CRISPR/Cas9 technology, and male transgenic PD/LBD mice, plus vetting in human postmortem brains (both male and female). We provide mechanistic insight into this pathologic pathway. We find that aberrant S-nitrosylation of the autophagic adaptor protein p62 causes inhibition of autophagic flux and intracellular buildup of misfolded proteins, with consequent secretion resulting in cell-to-cell spread. Thus, our data show that pathologic protein S-nitrosylation of p62 represents a critical factor not only for autophagic inhibition and demise of individual neurons, but also for α-syn release and spread of disease throughout the nervous system.
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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.