ArticleNeurobiology of disease2018
Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson's disease.
Article in Neurobiology of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 94 citations in OpenAlex.
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Identification of divergent organ-specific gene and protein expression signatures for mitochondrial function, inflammatory response, and proteostasis in the liver and brain in the rotenone-induced rat model of Parkinson's disease.Molecular biology reports · 2026Article
- Astrocytes in Parkinson's Disease: From Guardians to Accomplices.Clinical interventions in aging · 2026Review
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- Tetrahedral Framework Nucleic Acid-Based Delivery of DJ-1-saRNA Prevent Retinal Ischaemia-Reperfusion Injury via Inhibiting Ferroptosis.Cell proliferation · 2025Article
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Neuronal injury and hepatotoxicity: astrocytes and stellate cells convergence and their role in tissue repair.Frontiers in neuroscience · 2025Review
- Protective effects of enzymatically digested velvet antler polypeptides on mitochondria in primary astrocytes.Journal of animal science and technology · 2025Article
- Peptide Activator Stabilizes DJ-1 Structure and Enhances Its Activity.International journal of molecular sciences · 2024Article
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.Molecular neurobiology · 2024Article
- The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.Cell proliferation · 2024Article
- Knockdown of DJ-1 Resulted in a Coordinated Activation of the Innate Immune Antiviral Response in HEK293 Cell Line.International journal of molecular sciences · 2024Article
- LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants.Neurobiology of disease · 2024Article
- Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.Molecular neurobiology · 2024Article
- What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson's Disease?International journal of molecular sciences · 2024Review
- Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson's disease model.Nature communications · 2024Article
- The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection.CNS & neurological disorders drug targets · 2024Review
- Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.MedComm · 2023Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
DJ-1 is a redox-sensitive protein with several putative functions important in mitochondrial physiology, protein transcription, proteasome regulation, and chaperone activity. High levels of DJ-1 immunoreactivity are reported in astrocytes surrounding pathology associated with idiopathic Parkinson's disease, possibly reflecting the glial response to oxidative damage. Previous studies showed that astrocytic over-expression of DJ-1 in vitro prevented oxidative stress and mitochondrial dysfunction in primary neurons. Based on these observations, we developed a pseudotyped lentiviral gene transfer vector with specific tropism for CNS astrocytes in vivo to overexpress human DJ-1 protein in astroglial cells. Following vector delivery to the substantia nigra and striatum of adult Lewis rats, the DJ-1 transgene was expressed robustly and specifically within astrocytes. There was no observable transgene expression in neurons or other glial cell types. Three weeks after vector infusion, animals were exposed to rotenone to induce Parkinson's disease-like pathology, including loss of dopaminergic neurons, accumulation of endogenous α-synuclein, and neuroinflammation. Animals over-expressing hDJ-1 in astrocytes were protected from rotenone-induced neurodegeneration, and displayed a marked reduction in neuronal oxidative stress and microglial activation. In addition, α-synuclein accumulation and phosphorylation were decreased within substantia nigra dopaminergic neurons in DJ-1-transduced animals, and expression of LAMP-2A, a marker of chaperone mediated autophagy, was increased. Together, these data indicate that astrocyte-specific overexpression of hDJ-1 protects neighboring neurons against multiple pathologic features of Parkinson's disease and provides the first direct evidence in vivo of a cell non-autonomous neuroprotective function of astroglial DJ-1.
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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.