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

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 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

Язык: Английский

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

Ying Wang,

Yu Zhang

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2023, Номер 63(11), С. 3591 - 3600

Опубликована: Май 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

Язык: Английский

Процитировано

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

и другие.

Frontiers in Molecular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Сен. 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 (

Язык: Английский

Процитировано

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

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 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

Язык: Английский

Процитировано

0