ArticleGlia2022
Neurodegeneration and neuroinflammation are linked, but independent of alpha-synuclein inclusions, in a seeding/spreading mouse model of Parkinson's disease.
Article in Glia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Antidiabetic drugs in Parkinson's disease: a comprehensive meta-analysis on efficacy and safety with trial sequential analysis and GRADE evaluation.Inflammopharmacology · 2025Pooled it
- Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease.Frontiers in aging neuroscience · 2022Pooled it
- Inhibiting 15-PGDH restores redox homeostasis and confers neuroprotection in Parkinson's disease.Redox biology · 2026Article
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Article
- Multi-Omics Integrated Analysis Reveals Correlative Signatures of Short-Chain PFAS Mixtures on Mouse Midbrain Dopaminergic Neurons Involving the TM/5-HT Pathway.International journal of molecular sciences · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Article
- Neuroinflammatory Mechanisms and Vocalization Biomarkers in theMedical research archives · 2025Article
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
- Optical coherence tomography reveals retinal structural abnormalities in α-synucleinopathies: insights from the Padua-CESNE cohort.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Microglial dynamics and neuroinflammation in prodromal and early Parkinson's disease.Journal of neuroinflammation · 2025Review
- Alpha synuclein and inflammaging.Heliyon · 2025Review
- Protocol for immunofluorescence staining and large-scale analysis to quantify microglial cell morphology at single-cell resolution in mice.STAR protocols · 2024Article
- Novel tools to quantify total, phospho-Ser129 and aggregated alpha-synuclein in the mouse brain.NPJ Parkinson's disease · 2024Article
- Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.Molecular psychiatry · 2024Article
- Article
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Authors and funding
25 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A key pathological process in Parkinson's disease (PD) is the transneuronal spreading of α-synuclein. Alpha-synuclein (α-syn) is a presynaptic protein that, in PD, forms pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of α-syn particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used a model of spreading of α-syn induced by striatal injection of α-syn preformed fibrils into the mouse striatum to address this question. We performed quantitative analysis for α-syn inclusions, neurodegeneration, and microgliosis in different brain regions, and generated gene expression profiles of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also without α-syn inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. Using longitudinal gene expression profiling, we observed early gene expression changes, linked to neuroinflammation, that preceded neurodegeneration, indicating an active role of microglia in this process. Altered gene pathways overlapped with those typical of PD. Our observations indicate that α-syn inclusion formation is not the major driver in the early phases of PD-like neurodegeneration, but that microglia, activated by diffusible, oligomeric α-syn, may play a key role in this process. Our findings uncover new features of α-syn induced pathologies, in particular microgliosis, and point to the necessity for a broader view of the process of α-syn spreading.
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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.