ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
A53T human α-synuclein overexpression in transgenic mice induces pervasive mitochondria macroautophagy defects preceding dopamine neuron degeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 179 citations in OpenAlex.
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Association Between Blood-Brain Barrier Disruption and Gut Microbiota Dysbiosis in Parkinson's Disease.Cellular and molecular neurobiology · 2026Review
- 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
- Molecular mechanisms of exercise-induced neuroprotection against Parkinson's disease.Sports medicine and health science · 2026Review
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- PINK1 deficiency permits the development of Lewy body dementia with coexisting Aβ pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Imbalanced mitochondrial dynamics in human PD and α-synuclein mouse brains.Neurobiology of disease · 2025Article
- COVID-19 Alters Inflammatory, Mitochondrial, and Protein Clearance Pathway Genes: Potential Implications for New-onset Parkinsonism in Patients.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- The Mitochondrial Foundations of Parkinson's Disease: Therapeutic Implications.Aging and disease · 2025Review
- Immune cell metabolic dysfunction in Parkinson's disease.Molecular neurodegeneration · 2025Review
- Assessment of gastrointestinal function and enteric nervous system changes over time in the A53T mouse model of Parkinson's disease.Acta neuropathologica communications · 2025Article
- TFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease.Genes & diseases · 2025Article
- Preclinical studies and transcriptome analysis in a model of Parkinson's disease with dopaminergic ZNF746 expression.Molecular neurodegeneration · 2025Article
- Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.Biomedicines · 2025Review
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Loss of Nocturnin increases neuronal viability in oxidative stress conditions.Frontiers in neuroscience · 2025Article
- Mitophagy Upregulation Occurs Early in the Neurodegenerative Process Mediated by α-Synuclein.Molecular neurobiology · 2024Article
- α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- High frequency electrical stimulation reduces α-synuclein levels and α-synuclein-mediated autophagy dysfunction.Scientific reports · 2024Article
- Key genes and convergent pathogenic mechanisms in Parkinson disease.Nature reviews. Neuroscience · 2024Review
44 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
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Abstract
In vitro evidence suggests that the inefficient removal of damaged mitochondria by macroautophagy contributes to Parkinson's disease (PD). Using a tissue-specific gene amplification strategy, we generated a transgenic mouse line with human α-synuclein A53T overexpression specifically in dopamine (DA) neurons. Transgenic mice showed profound early-onset mitochondria abnormalities, characterized by macroautophagy marker-positive cytoplasmic inclusions containing mainly mitochondrial remnants, which preceded the degeneration of DA neurons. Genetic deletion of either parkin or PINK1 in these transgenic mice significantly worsened mitochondrial pathologies, including drastically enlarged inclusions and loss of total mitochondria contents. These data suggest that mitochondria are the main targets of α-synuclein and their defective autophagic clearance plays a significant role during pathogenesis. Moreover, endogenous PINK1 or parkin is indispensable for the proper autophagic removal of damaged mitochondria. Our data for the first time establish an essential link between mitochondria macroautophagy impairments and DA neuron degeneration in an in vivo model based on known PD genetics. The model, its well-defined pathologies, and the demonstration of a main pathogenesis pathway in the present study have set the stage and direction of emphasis for future studies.
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