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Updated: Feb 6, 2026

Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
Published on: June 25, 2019
A split biotin ligase approach reveals proteins associated with oligomeric alpha-synuclein during aggregation
Analiese R Fernandes1,2, Abigail P Owen2,3, Ayman H Faroqi1,2
1Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, USA.
Researchers identified proteins interacting with alpha-synuclein during early Lewy body disease stages. This discovery sheds light on potential mechanisms driving neurodegeneration in Lewy body diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Lewy body diseases are characterized by alpha-synuclein aggregation, but early cellular mechanisms remain poorly understood.
- Identifying proteins interacting with alpha-synuclein during initial aggregation stages is crucial for understanding disease initiation.
Purpose of the Study:
- To discover proteins that associate with monomeric and/or oligomeric alpha-synuclein during the early phases of aggregation.
- To elucidate cellular mechanisms underlying Lewy body pathology development.
Main Methods:
- Utilized a novel split biotin ligase assay fused to alpha-synuclein in cells treated with pre-formed fibrils.
- Employed BioSITe and mass spectrometry to identify alpha-synuclein interacting proteins under physiological and aggregated conditions.
Main Results:
- Identified 581 proteins differentiating interactions with monomeric versus multimeric alpha-synuclein.
- Revealed potential links to phosphorylation mechanisms, insulin processing, and the ALS/FTD-associated protein FUS.
- Highlighted potential loss of specific interactions contributing to sporadic Lewy body disease onset.
Conclusions:
- The study identified novel protein interactors of alpha-synuclein in early aggregation stages.
- Findings suggest potential roles for phosphorylation and insulin pathways, as well as FUS, in Lewy body pathogenesis.
- Loss of specific protein interactions may be a key factor in sporadic Lewy body diseases.
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