ArticlePloS one2015
Targeted Overexpression of α-Synuclein by rAAV2/1 Vectors Induces Progressive Nigrostriatal Degeneration and Increases Vulnerability to MPTP in Mouse.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Impact of aging on animal models of Parkinson's disease.Frontiers in aging neuroscience · 2022Pooled it
- Sex-Dependent Dynamics of Behavioural and Neuropathological Changes in an A53T Alpha-Synuclein Mouse Model of Parkinson's Disease.Cellular and molecular neurobiology · 2026Article
- Reduced rAAV interference enhances rcAAV detection sensitivity.Molecular therapy. Methods & clinical development · 2025Article
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
- Circadian clock dysfunction in Parkinson's disease: mechanisms, consequences, and therapeutic strategy.NPJ Parkinson's disease · 2025Review
- Vinpocetine and Lactobacillus Attenuated Rotenone-Induced Parkinson's Disease and Restored Dopamine Synthesis in Rats through Modulation of Oxidative Stress, Neuroinflammation, and Lewy Bodies Inclusion.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Malvidin-3-O-Glucoside Mitigates α-Syn and MPTP Co-Induced Oxidative Stress and Apoptosis in Human Microglial HMC3 Cells.International journal of molecular sciences · 2024Article
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Mitochondrial dysfunction in Parkinson's disease - a key disease hallmark with therapeutic potential.Molecular neurodegeneration · 2023Review
- Targeting Mitochondria as a Therapeutic Approach for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- Effects of levodopa on gut bacterial antibiotic resistance in Parkinson's disease rat.Frontiers in aging neuroscience · 2023Article
- NXP031 prevents dopaminergic neuronal loss and oxidative damage in the AAV-WT-α-synuclein mouse model of Parkinson's disease.PloS one · 2022Article
- Adeno-Associated Virus Expression of α-Synuclein as a Tool to Model Parkinson's Disease: Current Understanding and Knowledge Gaps.Aging and disease · 2021Review
- Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE.Heliyon · 2021Article
- The Role of Mitochondria in Neurodegenerative Diseases: the Lesson from Alzheimer's Disease and Parkinson's Disease.Molecular neurobiology · 2020Review
- Translation Imaging in Parkinson's Disease: Focus on Neuroinflammation.Frontiers in aging neuroscience · 2020Article
- Alpha-Synuclein Preserves Mitochondrial Fusion and Function in Neuronal Cells.Oxidative medicine and cellular longevity · 2019Article
- Removal of prolyl oligopeptidase reduces alpha-synuclein toxicity in cells and in vivo.Scientific reports · 2018Article
- α-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism.Molecular neurodegeneration · 2018Article
- Ceftriaxone Treatment for Neuronal Deficits: A Histological and MEMRI Study in a Rat Model of Dementia with Lewy Bodies.Behavioural neurology · 2018Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Mutations, duplication and triplication of α-synuclein genes are linked to familial Parkinson's disease (PD), and aggregation of α-synuclein (α-syn) in Lewy bodies (LB) is involved in the pathogenesis of the disease. The targeted overexpression of α-syn in the substantia nigra (SN) mediated by viral vectors may provide a better alternative to recapitulate the neurodegenerative features of PD. Therefore, we overexpressed human wild-type α-syn using rAAV2/1 vectors in the bilateral SN of mouse and examined the effects for up to 12 weeks. Delivery of rAAV-2/1-α-syn caused significant nigrostriatal degeneration including appearance of dystrophic striatal neurites, loss of nigral dopaminergic (DA) neurons and dissolving nigral neuron bodies in a time-dependent manner. In addition, the α-syn overexpressed mice also developed significant deficits in motor function at 12 weeks when the loss of DA neurons exceeded a threshold of 50%. To investigate the sensitivity to neurotoxins in mice overexpressing α-syn, we performed an MPTP treatment with the subacute regimen 8 weeks after rAAV injection. The impact of the combined genetic and environmental insults on DA neuronal loss, striatal dopamine depletion, dopamine turnover and motor dysfunction was markedly greater than that of either alone. Moreover, we observed increased phosphorylation (S129), accumulation and nuclear distribution of α-syn after the combined insults. In summary, these results reveal that the overexpressed α-syn induces progressive nigrostriatal degeneration and increases the susceptibility of DA neurons to MPTP. Therefore, the targeted overexpression of α-syn and the combination with environmental toxins may provide valuable models for understanding PD pathogenesis and developing related therapies.
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