Molecular rotors provide insight into the mechanism of formation and conversion ofα-synuclein aggregates DOI
Siân C. Allerton, Marina K. Kuimova, Francesco A. Aprile

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

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 but have poor sensitivity to early-stage, toxic oligomers. Molecular rotors are fluorophores sense changes viscosity their local environment. Here, we monitor -synuclein oligomer using fluorescence lifetime molecular rotors. We detect and conversion into for wild type two variants; pathological mutant A30P ΔP -synuclein, which lacks a master regulator region aggregation (residues 36-42). shows similar rate compared whereas delayed formation. Additionally, both variants demonstrate slower oligomers amyloids. Our method provides quantitative approach unveiling complex mechanism key understanding pathology

Language: Английский

Dissecting the Self-assembly Dynamics of Imperfect Repeats in α-Synuclein DOI
Fengjuan Huang,

Ying Wang,

Yu Zhang

et al.

Journal of Chemical Information and Modeling, Journal Year: 2023, Volume and Issue: 63(11), P. 3591 - 3600

Published: May 30, 2023

The pathological aggregation of α-synuclein (αS) into amyloid fibrils is the hallmark Parkinson's disease (PD). self-assembly and membrane interactions αS are mainly governed by seven imperfect 11-residue repeats XKTKEGVXXXX motif around residues 1-95. However, particular role each repeat in fibrillization remains unclear. To answer this question, we studied dynamics with up to 10 peptides

Language: Английский

Citations

14
A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson’s disease DOI Creative Commons
Ofir Sade,

Daphna Fischel,

Noa Barak-Broner

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Sept. 4, 2024

Alpha-synuclein (aSyn) aggregates in the central nervous system are main pathological hallmark of Parkinson's disease (PD). ASyn have also been detected many peripheral tissues, including skin, thus providing a novel and accessible target tissue for detection PD pathology. Still, well-established validated quantitative biomarker early diagnosis that allows tracking progression remains lacking. The goal this research was to characterize aSyn skin biopsies as comparative measure Using direct stochastic optical reconstruction microscopy (

Language: Английский

Citations

0
Molecular rotors provide insight into the mechanism of formation and conversion ofα-synuclein aggregates DOI
Siân C. Allerton, Marina K. Kuimova, Francesco A. Aprile

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

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 but have poor sensitivity to early-stage, toxic oligomers. Molecular rotors are fluorophores sense changes viscosity their local environment. Here, we monitor -synuclein oligomer using fluorescence lifetime molecular rotors. We detect and conversion into for wild type two variants; pathological mutant A30P ΔP -synuclein, which lacks a master regulator region aggregation (residues 36-42). shows similar rate compared whereas delayed formation. Additionally, both variants demonstrate slower oligomers amyloids. Our method provides quantitative approach unveiling complex mechanism key understanding pathology

Language: Английский

Citations

0