ArticleActa neuropathologica2016
Axonal transport and secretion of fibrillar forms of α-synuclein, Aβ42 peptide and HTTExon 1.
Article in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
92 citing papers in PubMed, 157 citations in OpenAlex.
- Activated microglial phenotypes in the hippocampal CA2 subfield are implicated in Lewy body disease progression.Acta neuropathologica · 2026Article
- Tear fluid as a novel specimen for detection of alpha-synuclein seeding activity in Parkinson's disease.Scientific 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
- Microfluidic platform for understanding Parkinson's disease and α-synuclein conformation.Translational neurodegeneration · 2025Review
- Intracellular Transport of Monomeric Peptides, (Poly)Peptide-Based Coacervates and Fibrils: Mechanisms and Prospects for Drug Delivery.International journal of molecular sciences · 2025Review
- A high-fidelity microfluidic platform reveals retrograde propagation as the main mechanism of α-Synuclein spread in human neurons.NPJ Parkinson's disease · 2025Article
- Lewy body diseases and the gut.Molecular neurodegeneration · 2025Review
- Prion and "Prion-Like" Detection: From Conventional Methods to Microfluidics or Lab-on-Chip Platforms to Monitor Seeding and Spreading of Misfolded Proteins.Sub-cellular biochemistry · 2025Review
- Fibrillar Alpha-Synuclein Alters the Intracellular Chaperone Levels within Hours of Its Internalization.ACS omega · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- The Expression and Functionality of CBInternational journal of molecular sciences · 2024Article
- Microfluidic compartmentalization of rat vagal afferent neurons to model gut-brain axis.Bioelectronic medicine · 2024Article
- Differentiation of Neurons, Astrocytes, Oligodendrocytes and Microglia From Human Induced Pluripotent Stem Cells to Form Neural Tissue-On-Chip: A Neuroinflammation Model to Evaluate the Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells.Stem cell reviews and reports · 2024Article
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- Synapses do not facilitate prion-like transfer of alpha-synuclein: a quantitative study in reconstructed unidirectional neural networks.Cellular and molecular life sciences : CMLS · 2023Article
- Synucleinopathies: Intrinsic and Extrinsic Factors.Cell biochemistry and biophysics · 2023Article
- Physiological Roles of β-amyloid in Regulating Synaptic Function: Implications for AD Pathophysiology.Neuroscience bulletin · 2023Review
- Review
- White and gray matter alterations in de novo PD patients: which matter most?Journal of neurology · 2023Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Accruing evidence suggests that prion-like behavior of fibrillar forms of α-synuclein, β-amyloid peptide and mutant huntingtin are responsible for the spread of the lesions that characterize Parkinson disease, Alzheimer disease and Huntington disease, respectively. It is unknown whether these distinct protein assemblies are transported within and between neurons by similar or distinct mechanisms. It is also unclear if neuronal death or injury is required for neuron-to-neuron transfer. To address these questions, we used mouse primary cortical neurons grown in microfluidic devices to measure the amounts of α-synuclein, Aβ42 and HTTExon1 fibrils transported by axons in both directions (anterograde and retrograde), as well as to examine the mechanism of their release from axons after anterograde transport. We observed that the three fibrils were transported in both anterograde and retrograde directions but with strikingly different efficiencies. The amount of Aβ42 fibrils transported was ten times higher than that of the other two fibrils. HTTExon1 was efficiently transported in the retrograde direction but only marginally in the anterograde direction. Finally, using neurons from two distinct mutant mouse strains whose axons are highly resistant to neurodegeneration (Wld(S) and Sarm1(-/-)), we found that the three different fibrils were secreted by axons after anterograde transport, in the absence of axonal lysis, indicating that trans-neuronal spread can occur in intact healthy neurons. In summary, fibrils of α-synuclein, Aβ42 and HTTExon1 are all transported in axons but in directions and amounts that are specific of each fibril. After anterograde transport, the three fibrils were secreted in the medium in the absence of axon lysis. Continuous secretion could play an important role in the spread of pathology between neurons but may be amenable to pharmacological intervention.
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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.