ArticleInternational journal of molecular sciences2020
Modeling Parkinson's Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers.
Article in International journal of molecular sciences, 2020. 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, 33 citations in OpenAlex.
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Retinal alterations resemble brain pathology in a rat model of Parkinson's disease induced by intranigral infusion of α-synuclein oligomers.Cell death discovery · 2025Article
- Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.Behavioral and brain functions : BBF · 2025Review
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Protein Misfolding in the Pathogenesis and Diagnosis of Neurodegenerative Diseases (Review).Sovremennye tekhnologii v meditsine · 2025Review
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- Immune responses to oligomeric α-synuclein in Parkinson's disease peripheral blood mononuclear cells.Journal of neurology · 2024Article
- "Prion-like" seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders.Frontiers in neuroscience · 2024Review
- α-Synuclein and biological membranes: the danger of loving too much.Chemical communications (Cambridge, England) · 2023Review
- Abnormal expression of fission and fusion genes and the morphology of mitochondria in eutopic and ectopic endometrium.European journal of medical research · 2023Article
- The Toxicity of Protein Aggregates: New Insights into the Mechanisms.International journal of molecular sciences · 2023Article
- Alpha Synuclein: Neurodegeneration and Inflammation.International journal of molecular sciences · 2023Review
- Article
- Spontaneous Object Exploration in a Recessive Gene Knockout Model of Parkinson's Disease: Development and Progression of Object Recognition Memory Deficits in MaleFrontiers in behavioral neuroscience · 2022Article
- Review
- Repurposing Pomalidomide as a Neuroprotective Drug: Efficacy in an Alpha-Synuclein-Based Model of Parkinson's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Cardiac Changes in Parkinson's Disease: Lessons from Clinical and Experimental Evidence.International journal of molecular sciences · 2021Review
- Neonatal Reserpine Administration Produces Widespread Neuronal Losses and ⍺-Synuclein Inclusions in a Rat Model.Neurotoxicity research · 2021Article
- Adeno-Associated Virus Expression of α-Synuclein as a Tool to Model Parkinson's Disease: Current Understanding and Knowledge Gaps.Aging and disease · 2021Review
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson's disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies.
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