ArticleThe Journal of clinical investigation2024
Deficiency of parkin causes neurodegeneration and accumulation of pathological α-synuclein in monkey models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- When copper turns killer: Decoding copper dyshomeostasis and cuproptosis in neurodegenerative pathogenesis and precision metal interventions.Neural regeneration research · 2026Article
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- The parkin-γ-tubulin axis regulates epidermal homeostasis and is associated with the susceptibility to psoriasis.Cell death and differentiation · 2026Article
- High molecular weight insoluble parkin in the substantia nigra of patients with idiopathic Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Neural cell state modulation bybioRxiv : the preprint server for biology · 2026Article
- Genetically Modified Primate Models for Brain Disorder Research.Neuroscience bulletin · 2026Review
- Establishment of a novel cynomolgus monkey model of hyperuricemia.Animal models and experimental medicine · 2026Article
- The Vesicular Glutamate Transporter Modulates Sex and Region-Specific Differences in Dopaminergic Neuron α-Synuclein Toxicity by Modifying Cytosolic Dopamine Levels.bioRxiv : the preprint server for biology · 2026Article
- Review
- Rethinking PINK1/Parkin-mediated mitophagy in Parkinson's disease: functional continuity and activation-clearance uncoupling.Frontiers in aging neuroscience · 2026Review
- Targeting mitochondrial autophagy for anti-aging.Cell death discovery · 2025Review
- SYK regulates Schwann cell metabolic reprogramming to promote axonal regeneration in immune-mediated neuropathy.Journal of neuroinflammation · 2025Article
- Regulation of UBC12 expression and protein neddylation by PINK1 suggests a primate-specific function.Zoological research · 2025Article
- Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease.Biomolecules · 2025Review
- Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges.Biomedicines · 2025Review
- Formation of seeding-competent α-synuclein aggregates in parkin-deficient iPSC-derived human neurons.NPJ Parkinson's disease · 2025Article
- Bridging the gap: investigating the role of phosphorylation at the serine 129 site of α-synuclein in VAPB-PTPIP51 interactions.Acta neuropathologica communications · 2025Article
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is characterized by age-dependent neurodegeneration and the accumulation of toxic phosphorylated α-synuclein (pS129-α-syn). The mechanisms underlying these crucial pathological changes remain unclear. Mutations in parkin RBR E3 ubiquitin protein ligase (PARK2), the gene encoding parkin that is phosphorylated by PTEN-induced putative kinase 1 (PINK1) to participate in mitophagy, cause early onset PD. However, current parkin-KO mouse and pig models do not exhibit neurodegeneration. In the current study, we utilized CRISPR/Cas9 technology to establish parkin-deficient monkey models at different ages. We found that parkin deficiency leads to substantia nigra neurodegeneration in adult monkey brains and that parkin phosphorylation decreases with aging, primarily due to increased insolubility of parkin. Phosphorylated parkin is important for neuroprotection and the reduction of pS129-α-syn. Consistently, overexpression of WT parkin, but not a mutant form that cannot be phosphorylated by PINK1, reduced the accumulation of pS129-α-syn. These findings identify parkin phosphorylation as a key factor in PD pathogenesis and suggest it as a promising target for therapeutic interventions.
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