ArticleCell death & disease2019
A30P mutant α-synuclein impairs autophagic flux by inactivating JNK signaling to enhance ZKSCAN3 activity in midbrain dopaminergic neurons.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Genetics of α-Synuclein: The Prime Pathological Player of Parkinson's Disease.Neurotoxicity research · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Neuroprotective effect of sigma-1-receptor agonist 1,3-di-o-tolylguanidine in rotenone-induced model of Parkinson's disease in rats.Metabolic brain disease · 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
- Breaking the proteasome balance: α-synuclein and the ubiquitin-proteasome system.Frontiers in cell and developmental biology · 2026Review
- Inherited Genetic Variation in Parkinson's Disease: Convergence on Impaired Autophagosome-Lysosome Fusion Through the Altered Expression of mRNA Isoforms.Molecular neurobiology · 2025Article
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Research Progress on the Functional Regulation Mechanisms of ZKSCAN3.Biomolecules · 2025Review
- Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease.Biomedical reports · 2025Article
- High-resolution Cryo-EM Structure Determination of a-Synuclein-A Prototypical Amyloid Fibril.Bio-protocol · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.Autophagy reports · 2025Review
- Subtle concentration changes in zinc hold the key to fibrillation of α-synuclein: an updated insight on the micronutrient's role in prevention of neurodegenerative disorders.Frontiers in molecular biosciences · 2025Review
- The interplay between physical exercise and autophagy signaling in brain health, neurodegenerative diseases and aging.Frontiers in aging neuroscience · 2025Review
- Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson's disease and parkinsonism-dementia of Guam.Cell death & disease · 2024Article
- The Biological Roles of ZKSCAN3 (ZNF306) in the Hallmarks of Cancer: From Mechanisms to Therapeutics.International journal of molecular sciences · 2024Review
- High-Resolution Cryo-EM Structure Determination of α-synuclein - A Prototypical Amyloid Fibril.bioRxiv : the preprint server for biology · 2024Article
- Emerging roles of SIRT1 activator, SRT2104, in disease treatment.Scientific reports · 2024Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in α-synuclein gene have been linked to familial early-onset Parkinson's disease (PD) with Lewy body pathology. A30P mutant α-synuclein is believed to suppress autophagic progression associated with PD pathogenesis. However, the mechanistic link between A30P mutation and autophagy inhibition in PD remains poorly understood. In this study, we identified that A30P mutant α-synuclein resulted in reduced autophagy flux through promoting the decrease of autophagosomal membrane-associated protein LC3 and the increase of SQSTM1/p62 protein levels in midbrain dopaminergic neuron, due to the transcriptional repressor ZKSCAN3 trafficking from the cytoplasm to the nucleus. Moreover, the results demonstrated that A30P mutant α-synuclein not only decreased the phospho-c-Jun N-terminal Kinase (p-JNK) levels in midbrain dopaminergic neuron but also interfered autophagy without influencing the activities of AMPK and mTOR. Collectively, the present study reveals a novel autophagy inhibition mechanism induced by A30P mutant α-synuclein via transcriptional activation of the ZKSCAN3 in a JNK-dependent manner.
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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.