# Molecular Rotors Detect the Formation and Conversion of α-Synuclein Oligomers

## TL;DR

Researchers developed a new method using molecular rotors to detect early-stage α-synuclein oligomers linked to Parkinson’s disease.

## Contribution

A novel fluorescence-based method to detect α-synuclein oligomer formation and conversion into amyloids.

## Key findings

- A30P α-synuclein forms oligomers at a rate similar to wild-type α-synuclein.
- ΔP1 α-synuclein shows delayed oligomer formation and slower conversion to amyloids.
- Molecular rotors provide a quantitative way to study α-synuclein aggregation mechanisms.

## Abstract

α-Synuclein is an intrinsically disordered protein
that forms
amyloids in Parkinson’s disease. Currently, detection methods
predominantly report on the formation of mature amyloids but are weakly
sensitive to the early stage, toxic oligomers. Molecular rotors are
fluorophores that sense changes in the viscosity of their local environment.
Here, we monitor α-synuclein oligomer formation using the fluorescence
lifetime of molecular rotors. We detect oligomer formation and conversion
into amyloids for wild-type and two α-synuclein variants, the
pathological mutant A30P and ΔP1 α-synuclein, which lacks
a master regulator region of aggregation (residues 36–42).
We report that A30P α-synuclein shows a rate of oligomer formation
similar to that of wild-type α-synuclein, whereas ΔP1
α-synuclein shows delayed oligomer formation. Additionally,
both variants demonstrate a slower conversion of oligomers into amyloids.
Our method provides a quantitative approach to unveiling the complex
mechanism of α-synuclein aggregation, which is key to understanding
the pathology of Parkinson’s disease.