ArticleNPJ Parkinson's disease2025
Parkinson's paradox: alpha-synuclein's selective strike on SNc dopamine neurons over VTA.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Therapeutics candidates and repurposing strategies to target parkinson's disease pathology: current evidence and future directions.Metabolic brain disease · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- α-Synuclein pathology differentially alters T-type calcium currents in vulnerable and resilient substantia nigra dopaminergic subpopulations.bioRxiv : the preprint server for biology · 2026Article
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Age-related dopaminergic integrity in the SNpc and VTA: morphometric and volumetric findings in marmoset (Frontiers in neuroanatomy · 2026Article
- Towards a Biologically Defined Diagnosis: Incorporating Pathophysiological Measures Into Parkinson's Disease Clinical Criteria.Parkinson's disease · 2026Review
- Apathy and Reduced Voluntary Activity in Older Adults with Parkinson's Disease: Mechanisms, Clinical Assessment, and Rehabilitation Implications.Clinical interventions in aging · 2026Review
- PRMT1 in Health and Disease: Emerging Perspectives From Molecular Mechanisms to Therapeutic Strategies.MedComm · 2025Review
- miR-218 Regulates the Excitability of VTA Dopamine Neurons and the Mesoaccumbens Pathway in Mice.Brain sciences · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
A central question in Parkinson's disease (PD) and related synucleinopathies research is why dopamine neurons in the substantia nigra pars compacta (SNc) are more vulnerable than those in the ventral tegmental area (VTA). We investigated how α-synuclein affects neuronal activity before cell death using two mouse models: α-synuclein preformed fibril injections and AAV-mediated human α-synuclein expression. Four-weeks post-injection, histological analysis confirmed no significant neuronal loss in either structure, providing a temporal window to study neuronal activity before cell death. Electrophysiological recordings revealed region-specific vulnerability: SNc dopamine neurons exhibited significantly increased baseline firing rates while VTA neurons remained unaffected. SNc neurons showed impaired homeostatic firing regulation following hyperpolarization, while VTA neurons maintained normal recovery. Elevated α-synuclein also altered network stability in SNc dopamine neurons before cell death, while sparing VTA neurons. These findings reveal early functional differences that may explain the selective vulnerability of SNc dopamine neurons in PD.
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Registered trials
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.