ArticleMolecular biomedicine2024
Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson's disease.
Article in Molecular biomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Severity-dependent changes in hippocampal necroptosis markers and neuronal loss in a PTSD-like mouse model: potential involvement of nitric oxide signaling.Psychopharmacology · 2026Article
- Low-intensity transcranial ultrasound neuromodulation promotes neuronal regeneration: A new hope for noninvasive treatment of neurodegenerative diseases.Neural regeneration research · 2026Article
- Neurotransmitter Dysregulation in Parkinson's Disease: Pathophysiological Insights and Therapeutic Perspectives.ACS chemical neuroscience · 2026Review
- Engineered Source-Specific Extracellular Vesicles for Neurodegenerative Diseases: From Biological Barriers to Targeted Delivery Strategies.International journal of nanomedicine · 2026Review
- Unveiling Exosomes and Microvesicles in Parkinson's Disease: Mechanistic Insights Into Cell Death Pathways and Therapeutic Potential.Molecular neurobiology · 2025Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Review
- Protective effects of paederoside in rotenone-induced cellular models of Parkinson's disease.Frontiers in cell and developmental biology · 2025Article
- Oxidative cell death in the central nervous system: mechanisms and therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- A primary rat neuron-astrocyte-microglia tri-culture model for studying mechanisms of neurotoxicity.Frontiers in toxicology · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
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Abstract
Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.
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