ArticleCommunications biology2022
C-terminal truncation modulates α-Synuclein's cytotoxicity and aggregation by promoting the interactions with membrane and chaperone.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- A Systematic Review on Disease-Modifying Therapies in Parkinsonian Disorders.Clinical pharmacology and therapeutics · 2026Pooled it
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.Autophagy · 2026Article
- Transient Interactions of α-Synuclein N- and C-Termini.ACS chemical neuroscience · 2026Article
- The disordered and structured regions ofbioRxiv : the preprint server for biology · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Cross-Linking and Covalent Labeling Mass Spectrometry Reveal Proteoform-Driven Conformational Changes in Alpha Synuclein.Analytical chemistry · 2026Article
- Water Accelerates in the Hydration Shell of the N- and C-Terminal Domains of α-Synuclein in the Presence of NaCl.The journal of physical chemistry. B · 2026Article
- Parkinson's disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions.Communications biology · 2026Article
- Thermodynamic stability modulates chaperone-mediated disaggregation of α-synuclein fibrils.Chemical science · 2026Article
- Visualizing liquid-liquid phase separation and protein aggregates.Communications chemistry · 2025Review
- Molecular Dynamics Study of α-Synuclein Domain Deletion Mutant Monomers.Biomolecules · 2025Article
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- "Coordination of Anle138b to Silver Results in Selective Reduction of a C-terminal truncated Alpha-synuclein Protein and Increased Aggregate Size."bioRxiv : the preprint server for biology · 2025Article
- Interaction Between α-Synuclein and DJ-1 in Parkinson's Disease.Brain sciences · 2025Review
- Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.Nature communications · 2025Article
- Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease.Nature communications · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- The interplay of iron, oxidative stress, and α-synuclein in Parkinson's disease progression.Molecular medicine (Cambridge, Mass.) · 2025Review
- Alpha-Synuclein Pathophysiology in Neurodegenerative Disorders: A Review Focusing on Molecular Mechanisms and Treatment Advances in Parkinson's Disease.Cellular and molecular neurobiology · 2025Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
α-Synuclein (α-syn) is the main protein component of Lewy bodies, the major pathological hallmarks of Parkinson's disease (PD). C-terminally truncated α-syn is found in the brain of PD patients, reduces cell viability and tends to form fibrils. Nevertheless, little is known about the mechanisms underlying the role of C-terminal truncation on the cytotoxicity and aggregation of α-syn. Here, we use nuclear magnetic resonance spectroscopy to show that the truncation alters α-syn conformation, resulting in an attractive interaction of the N-terminus with membranes and molecular chaperone, protein disulfide isomerase (PDI). The truncated protein is more toxic to mitochondria than full-length protein and diminishes the effect of PDI on α-syn fibrillation. Our findings reveal a modulatory role for the C-terminus in the cytotoxicity and aggregation of α-syn by interfering with the N-terminus binding to membranes and chaperone, and provide a molecular basis for the pathological role of C-terminal truncation in PD pathogenesis.
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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.