ArticleActa neuropathologica communications2020
Trans-synaptic and retrograde axonal spread of Lewy pathology following pre-formed fibril injection in an in vivo A53T alpha-synuclein mouse model of synucleinopathy.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
- Genetics of α-Synuclein: The Prime Pathological Player of Parkinson's Disease.Neurotoxicity research · 2026Review
- Activated microglial phenotypes in the hippocampal CA2 subfield are implicated in Lewy body disease progression.Acta neuropathologica · 2026Article
- Connexin 50 mediates disease-relevant alpha-synuclein oligomer propagation and neuroinflammation in neurodegenerative disease.iScience · 2026Article
- Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic.Nature structural & molecular biology · 2026Review
- Live cell imaging of exogenous α-synuclein fibrils in primary microglia and neuron co-cultures.Biochemistry and biophysics reports · 2026Article
- Microglial reactivity in the hippocampal CA2 is associated with advanced neuronal α-synucleinopathy.bioRxiv : the preprint server for biology · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Direct current stimulation induced reduction in α-synuclein in primary neurons: targeting Parkinson's disease.Brain communications · 2026Article
- Aquaporin-4 mis-localization decreases glymphatic clearance of α-synuclein in an alpha-syntrophin knock out mouse model and promotes α-synuclein pathology and aggregate propagation.Brain communications · 2026Article
- The extent of alpha-synuclein aggregate accumulation in neurons varies depending on the type of neurotransmitter they release.Scientific reports · 2025Article
- 14-3-3θ phosphorylation at S232 reduces its interactome and regulates axonal trafficking.Disease models & mechanisms · 2025Article
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- Alpha-synuclein overexpression does not cause vocalization deficits in a mouse model of parkinsonism.Biology open · 2025Article
- Proteomic and phosphoproteomic signatures of aging mouse liver.GeroScience · 2025Article
- A high-fidelity microfluidic platform reveals retrograde propagation as the main mechanism of α-Synuclein spread in human neurons.NPJ Parkinson's disease · 2025Article
- Astrocytic RNA editing regulates the host immune response to alpha-synuclein.Science advances · 2025Article
- Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Rotenone accelerates endogenous α-synuclein spreading and enhances neurodegeneration in an intra-striatal α-synuclein preformed fibril injected mouse model of Parkinson's disease.Frontiers in cellular neuroscience · 2025Article
- The interplay between α-synuclein aggregation and necroptosis in Parkinson's disease: a spatiotemporal perspective.Frontiers in neuroscience · 2025Review
- Current insights and assumptions on α-synuclein in Lewy body disease.Acta neuropathologica · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
It is necessary to develop an understanding of the specific mechanisms involved in alpha-synuclein aggregation and propagation to develop disease modifying therapies for age-related synucleinopathies, including Parkinson's disease and Dementia with Lewy Bodies. To adequately address this question, we developed a new transgenic mouse model of synucleinopathy that expresses human A53T SynGFP under control of the mouse prion protein promoter. Our characterization of this mouse line demonstrates that it exhibits several distinct advantages over other, currently available, mouse models. This new model allows rigorous study of the initial location of Lewy pathology formation and propagation in the living brain, and strongly suggests that aggregation begins in axonal structures with retrograde propagation to the cell body. This model also shows expeditious development of alpha-synuclein pathology following induction with small, in vitro-generated alpha-synuclein pre-formed fibrils (PFFs), as well as accelerated cell death of inclusion-bearing cells. Using this model, we found that aggregated alpha-synuclein somatic inclusions developed first in neurons, but later showed a second wave of inclusion formation in astrocytes. Interestingly, astrocytes appear to survive much longer after inclusion formation than their neuronal counterparts. This model also allowed careful study of peripheral-to-central spread of Lewy pathology after PFF injection into the hind limb musculature. Our results clearly show evidence of progressive, retrograde trans-synaptic spread of Lewy pathology through known neuroanatomically connected pathways in the motor system. As such, we have developed a promising tool to understand the biology of neurodegeneration associated with alpha-synuclein aggregation and to discover new treatments capable of altering the neurodegenerative disease course of synucleinopathies.
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