ArticleNature communications2020
Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease.Pharmaceutical research · 2026Article
- Seeing the Unseen: Super-Resolution Microscopy in Protein Aggregation Research.Chemical & biomedical imaging · 2026Review
- Review
- Brain Extracellular Space: From an Overlooked Dimension to Catalyst of a Novel Neuroscience Paradigm.Cyborg and bionic systems (Washington, D.C.) · 2026Review
- Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy.Frontiers in pharmacology · 2026Review
- Nanoscopic Mapping of the Extracellular Space in Amyloid Plaque-rich Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Midbrain extracellular matrix and microglia are associated with cognition in aging mice.Nature communications · 2025Article
- Alzheimer's Tau seeds-induced pathology enhances hippocampal extracellular diffusion.Communications biology · 2025Article
- Article
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Differential pathological dynamics triggered by distinct Parkinson patient-derived α-synuclein extracts in nonhuman primates.Science advances · 2025Article
- Transport in the brain studied withNeurophotonics · 2025Review
- Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition.Biophysical journal · 2025Article
- Microglial depletion increases aggrecan and hyaluronan levels in the diffuse and aggregated extracellular matrix of the mouse brain.Scientific reports · 2025Article
- Age-dependent progression from clearance to vulnerability in the early response of periventricular microglia to α-synuclein toxic species.Molecular neurodegeneration · 2025Article
- Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- Intracellular α-synuclein assemblies are sufficient to alter nanoscale diffusion in the striatal extracellular space.NPJ Parkinson's disease · 2024Article
- High-fidelity predictions of diffusion in the brain microenvironment.Biophysical journal · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, exploration of the brain extracellular space (ECS) has made remarkable progress, including nanoscopic characterizations. However, whether ECS precise conformation is altered during brain pathology remains unknown. Here we study the nanoscale organization of pathological ECS in adult mice under degenerative conditions. Using electron microscopy in cryofixed tissue and single nanotube tracking in live brain slices combined with super-resolution imaging analysis, we find enlarged ECS dimensions and increased nanoscale diffusion after α-synuclein-induced neurodegeneration. These animals display a degraded hyaluronan matrix in areas close to reactive microglia. Furthermore, experimental hyaluronan depletion in vivo reduces dopaminergic cell loss and α-synuclein load, induces microgliosis and increases ECS diffusivity, highlighting hyaluronan as diffusional barrier and local tissue organizer. These findings demonstrate the interplay of ECS, extracellular matrix and glia in pathology, unraveling ECS features relevant for the α-synuclein propagation hypothesis and suggesting matrix manipulation as a disease-modifying strategy.
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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.