ArticleCell death and differentiation2014
GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 72 citations in OpenAlex.
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- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Interplay of α-Synuclein Oligomers and Endoplasmic Reticulum Stress in Parkinson'S Disease: Insights into Cellular Dysfunctions.Inflammation · 2025Review
- Dopamine Toxicity Induces ROS-Dependent Death of Murine Neuroblastoma Cells: Impact on the Interactions of Cofilin With UCHL1 and MMP9.Neurochemical research · 2025Article
- The interaction of GRP78 and Zika virus E and NS1 proteins occurs in a chaperone-client manner.Scientific reports · 2024Article
- α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPCell death & disease · 2024Article
- Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us.Cerebellum (London, England) · 2024Review
- Review
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.Journal of virology · 2023Article
- Circular RNAs in Parkinson's Disease: Reliable Biological Markers and Targets for Rehabilitation.Molecular neurobiology · 2023Article
- LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.Cells · 2023Review
- β-Actin: An Emerging Biomarker in Ischemic Stroke.Cellular and molecular neurobiology · 2023Review
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Mycoplasma hyopneumoniae membrane protein Mhp271 interacts with host UPR protein GRP78 to facilitate infection.Molecular microbiology · 2022Article
- Cofilin Signaling in the CNS Physiology and Neurodegeneration.International journal of molecular sciences · 2021Review
- Correlative nanoscopy: A multimodal approach to molecular resolution.Microscopy research and technique · 2021Review
- How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases.International journal of molecular sciences · 2021Review
- Impact of Experimental Parameters on Cell-Cell Force Spectroscopy Signature.Sensors (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Mutation or multiplication of the alpha-synuclein (Syn)-encoding gene is frequent cause of early onset Parkinson's disease (PD). Recent evidences point to the pathogenic role of excess Syn also in sporadic PD. Syn is a cytosolic protein, which has been shown to be released from neurons. Here we provide evidence that extracellular Syn induces an increase in surface-exposed glucose-related protein of 78 kDa (GRP78), which becomes clustered in microdomains of the neuronal plasma membrane. Upon interacting with Syn, GRP78 activates a signaling cascade leading to cofilin 1 inactivation and stabilization of microfilaments, thus affecting morphology and dynamics of actin cytoskeleton in cultured neurons. Downregulation of GRP78 abolishes the activity of exogenous Syn, indicating that it is the primary target of Syn. Inactivation of cofilin 1 and stabilization of actin cytoskeleton are present also in fibroblasts derived from genetic PD patients, which show a dramatic increase in stress fibers. Similar changes are displayed by control cells incubated with the medium of PD fibroblasts, only when Syn is present. The accumulation of Syn in the extracellular milieu, its interaction with the plasma membrane and Syn-driven clustering of GRP78 appear, therefore, responsible for the dysregulation of actin turnover, leading to early deficits in synaptic function that precede neurodegeneration.
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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.