Article

A novel mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein fibrils and recapitulates its pathological diversity

2021-11-21

Abstract excerpt

A novel mutation (E83Q), the first in the NAC domain of alpha-synuclein (aSyn), was recently identified in a patient with dementia with Lewy bodies. We investigated the effects of this mutation on the aggregation of aSyn monomers and the structure, morphology, dynamic, and seeding activity of the aSyn fibrils in neurons. We found that it dramatically accelerates aSyn fibrillization and results in the formation of...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 51c02e8b-9e35-539b-b9d1-7efe76b11fc8
DOI: 10.1101/2021.11.21.469421

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

A novel mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein fibrils and recapitulates its pathological diversityDOI 10.1101/2021.11.21.469421Read

A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity.Semantic proximity Read

Recapitulating Parkinson’s pathology in human iPSC dopaminergic neurons reveals new mechanistic insights into Lewy body formation and heterogeneitySemantic proximity Read

A targetable N-terminal motif orchestrates α-Synuclein oligomer to fibril conversionSemantic proximity Read

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disordersSemantic proximity Read

Cryo-EM structure of α-Synuclein Fibrils Harboring the Dementia with Lewy Bodies–Associated E83Q MutationSemantic proximity Read

A novel alpha-synuclein K58N missense variant in a patient with Parkinson’s diseaseSemantic proximity Read

The effects of the novel A53E alpha-synuclein mutation on its oligomerization and aggregationSemantic proximity Read

Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body DisordersSemantic proximity Read

Targeting Hydrophobic Residues in the Alpha-Synuclein NAC Domain Disrupts Aggregation and Seed-Competent Fibril FormationSemantic proximity Read

Neuropathology, Genetics and Biomarkers of SynucleinopathiesSemantic proximity Read

Alpha-Synuclein Aggregation and Spread: Implications for the Pathology and Progression of Neurodegenerative DiseasesSemantic proximity Read

Secondary nucleation of α-Synuclein drives Mitochondria dysfunctions and Lewy body formation in Parkinson’s DiseaseSemantic proximity Read