ArticleMolecular neurodegeneration2015
SOD1 protein aggregates stimulate macropinocytosis in neurons to facilitate their propagation.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.Neurobiology of disease · 2026Article
- Trimeric superoxide dismutase 1 antibody as a universal biomarker for ALS.Research square · 2025Article
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
- High-content analysis of proteostasis capacity in cellular models of amyotrophic lateral sclerosis (ALS).Scientific reports · 2024Article
- Meiotic resetting of the cellular Sod1 pool is driven by protein aggregation, degradation, and transient LUTI-mediated repression.The Journal of cell biology · 2023Article
- P2X7 receptor activation mediates superoxide dismutase 1 (SOD1) release from murine NSC-34 motor neurons.Purinergic signalling · 2022Article
- Research progress on vesicular trafficking in amyotrophic lateral sclerosis.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Fcγ Receptor-Dependent Internalization and Off-Target Cytotoxicity of Antibody-Drug Conjugate Aggregates.Pharmaceutical research · 2022Article
- Hunting for the cause: Evidence for prion-like mechanisms in Huntington's disease.Frontiers in neuroscience · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
- Prospects on the nano-plastic particles internalization and induction of cellular response in human keratinocytes.Particle and fibre toxicology · 2021Article
- Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis.The EMBO journal · 2021Review
- A Metal-Free, Disulfide Oxidized Form of Superoxide Dismutase 1 as a Primary Misfolded Species with Prion-Like Properties in the Extracellular Environments Surrounding Motor Neuron-Like Cells.International journal of molecular sciences · 2021Article
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- Mutant Cu/Zn Superoxide Dismutase (A4V) Turnover Is Altered in Cells Containing Inclusions.Frontiers in molecular neuroscience · 2021Article
- Possible Mechanisms of Tau Spread and Toxicity in Alzheimer's Disease.Frontiers in cell and developmental biology · 2021Review
- LRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes.The EMBO journal · 2020Article
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16 authors.
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Abstract
backgroundAmyotrophic Lateral Sclerosis is characterized by a focal onset of symptoms followed by a progressive spread of pathology that has been likened to transmission of infectious prions. Cell-to-cell transmission of SOD1 protein aggregates is dependent on fluid-phase endocytosis pathways, although the precise molecular mechanisms remain to be elucidated.
resultsWe demonstrate in this paper that SOD1 aggregates interact with the cell surface triggering activation of Rac1 and subsequent membrane ruffling permitting aggregate uptake via stimulated macropinocytosis. In addition, other protein aggregates, including those associated with neurodegenerative diseases (TDP-43, Httex146Q, α-synuclein) also trigger membrane ruffling to gain entry into the cell. Aggregates are able to rupture unstructured macropinosomes to enter the cytosol allowing propagation of aggregation to proceed.
conclusionThus, we conclude that in addition to basic proteostasis mechanisms, pathways involved in the activation of macropinocytosis are key determinants in the spread of pathology in these misfolding diseases.
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