ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Brain injection of α-synuclein induces multiple proteinopathies, gliosis, and a neuronal injury marker.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Cerebrospinal fluid levels of neurofilament light chain in multiple system atrophy relative to Parkinson's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Pooled it
- Gut-initiated alpha synuclein fibrils drive parkinsonism phenotypes: temporal mapping of REM sleep behavior disorder-like and other non-motor symptoms.Translational neurodegeneration · 2026Article
- Understanding the Pre-Clinical Stages of Parkinson's Disease: Where Are We in Clinical and Research Settings?International journal of molecular sciences · 2025Review
- Female mice exhibit resistance to disease progression despite early pathology in a transgenic mouse model inoculated with alpha-synuclein fibrils.Communications biology · 2025Article
- Peripherin, A New Promising Biomarker in Neurological Disorders.The European journal of neuroscience · 2025Review
- The Type III Intermediate Filament Protein Peripherin Regulates Lysosomal Degradation Activity and Autophagy.International journal of molecular sciences · 2025Article
- Protein aggregates and biomolecular condensates: implications for human health and disease.Frontiers in molecular biosciences · 2025Review
- Advances in understanding the function of alpha-synuclein: implications for Parkinson's disease.Brain : a journal of neurology · 2023Review
- Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.Journal of neurology · 2023Article
- Cellular processing of α-synuclein fibrils results in distinct physiological C-terminal truncations with a major cleavage site at residue Glu 114.The Journal of biological chemistry · 2023Article
- Intrastriatal injection of Parkinson's disease intestine and vagus lysates initiates α-synucleinopathy in rat brain.Cell death & disease · 2023Article
- Inflammation promotes synucleinopathy propagation.Experimental & molecular medicine · 2022Article
- Pathogenesis of α-Synuclein in Parkinson's Disease: From a Neuron-Glia Crosstalk Perspective.International journal of molecular sciences · 2022Review
- Leveraging the preformed fibril model to distinguish between alpha-synuclein inclusion- and nigrostriatal degeneration-associated immunogenicity.Neurobiology of disease · 2022Review
- Unique seeding profiles and prion-like propagation of synucleinopathies are highly dependent on the host in human α-synuclein transgenic mice.Acta neuropathologica · 2022Article
- Analysis of hemisphere-dependent effects of unilateral intrastriatal injection of α-synuclein pre-formed fibrils on mitochondrial protein levels, dynamics, and function.Acta neuropathologica communications · 2022Article
- Neurofilament light as a biomarker for motor decline in Parkinson's disease.Frontiers in neuroscience · 2022Article
- Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies.Frontiers in neurology · 2022Review
- Evidence of Inflammation in Parkinson's Disease and Its Contribution to Synucleinopathy.Journal of movement disorders · 2022Article
- Rapid Induction of Dopaminergic Neuron Loss Accompanied by Lewy Body-Like Inclusions in A53T BAC-SNCA Transgenic Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Intracerebral injection of amyloidogenic α-synuclein (αS) has been shown to induce αS pathology in the CNS of nontransgenic mice and αS transgenic mice, albeit with varying efficiencies. In this study, using wild-type human αS transgenic mice (line M20), we demonstrate that intracerebral injection of recombinant amyloidogenic or soluble αS induces extensive αS intracellular inclusion pathology that is associated with robust gliosis. Near the injection site, a significant portion of αS inclusions are detected in neurons but also in astrocytes and microglia. Aberrant induction of expression of the intermediate filament protein peripherin, which is associated with CNS neuronal injury, was also observed predominantly near the site of injection. In addition, many pSer129 αS-induced inclusions colocalize with the low-molecular-mass neurofilament subunit (NFL) or peripherin staining. αS inclusion pathology was also induced in brain regions distal from the injection site, predominantly in neurons. Unexpectedly, we also find prominent p62-immunoreactive, αS-, NFL-, and peripherin-negative inclusions. These findings provide evidence that exogenous αS challenge induces αS pathology but also results in the following: (1) a broader disruption of proteostasis; (2) glial activation; and (3) a marker of a neuronal injury response. Such data suggest that induction of αS pathology after exogenous seeding may involve multiple interdependent mechanisms.
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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.