ArticleActa neuropathologica communications2017
Endosulfine-alpha inhibits membrane-induced α-synuclein aggregation and protects against α-synuclein neurotoxicity.
Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Emerging links between pediatric lysosomal storage diseases and adult parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2019Pooled it
- Co-expression-wide association studies link genetically regulated interactions with complex traits.Nature communications · 2025Article
- Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies.Cellular and molecular life sciences : CMLS · 2022Review
- Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders.Frontiers in aging neuroscience · 2021Review
- Article
- Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein.Molecular neurodegeneration · 2020Article
- Calcein Release Assay to Measure Membrane Permeabilization by Recombinant Alpha-Synuclein.Bio-protocol · 2020Article
- Initiation and propagation of α-synuclein aggregation in the nervous system.Molecular neurodegeneration · 2020Review
- Targeting α-synuclein for PD Therapeutics: A Pursuit on All Fronts.Biomolecules · 2020Review
- Assembly of α-synuclein aggregates on phospholipid bilayers.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- Alpha-Synuclein Is a Target of Fic-Mediated Adenylylation/AMPylation: Possible Implications for Parkinson's Disease.Journal of molecular biology · 2019Article
- The Roles of Post-translational Modifications on α-Synuclein in the Pathogenesis of Parkinson's Diseases.Frontiers in neuroscience · 2019Review
- Membranes as modulators of amyloid protein misfolding and target of toxicity.Biochimica et biophysica acta. Biomembranes · 2018Review
- The Oncogenic Functions of MASTL Kinase.Frontiers in cell and developmental biology · 2018Review
- In utero delivery of rAAV2/9 induces neuronal expression of the transgene in the brain: towards new models of Parkinson's disease.Gene therapy · 2017Article
- Alpha-synuclein oligomers: a new hope.Acta neuropathologica · 2017Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in the pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Evidence suggests that the self-assembly of aSyn conformers bound to phospholipid membranes in an aggregation-prone state plays a key role in aSyn neurotoxicity. Accordingly, we hypothesized that protein binding partners of lipid-associated aSyn could inhibit the formation of toxic aSyn oligomers at membrane surfaces. To address this hypothesis, we characterized the protein endosulfine-alpha (ENSA), previously shown to interact selectively with membrane-bound aSyn, in terms of its effects on the membrane-induced aggregation and neurotoxicity of two familial aSyn mutants, A30P and G51D. We found that wild-type ENSA, but not the non-aSyn-binding S109E variant, interfered with membrane-induced aSyn self-assembly, aSyn-mediated vesicle disruption and aSyn neurotoxicity. Immunoblotting analyses revealed that ENSA was down-regulated in the brains of synucleinopathy patients versus non-diseased individuals. Collectively, these results suggest that ENSA can alleviate neurotoxic effects of membrane-bound aSyn via an apparent chaperone-like activity at the membrane surface, and a decrease in ENSA expression may contribute to aSyn neuropathology in synucleinopathy disorders. More generally, our findings suggest that promoting interactions between lipid-bound, amyloidogenic proteins and their binding partners is a viable strategy to alleviate cytotoxicity in a range of protein misfolding disorders.
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