α-Synuclein pathology as a target in neurodegenerative diseases

H Park, TI Kam, VL Dawson, TM Dawson - Nature Reviews Neurology, 2024 - nature.com
Abstract α-Synuclein misfolds into pathological forms that lead to various neurodegenerative
diseases known collectively as α-synucleinopathies. In this Review, we provide a …

Flanking regions, amyloid cores, and polymorphism: the potential interplay underlying structural diversity

AA Bhopatkar, R Kayed - Journal of Biological Chemistry, 2023 - ASBMB
The β-sheet–rich amyloid core is the defining feature of protein aggregates associated with
neurodegenerative disorders. Recent investigations have revealed that there exist multiple …

Mass photometric detection and quantification of nanoscale α-synuclein phase separation

S Ray, TO Mason, L Boyens-Thiele, A Farzadfard… - Nature …, 2023 - nature.com
Protein liquid–liquid phase separation can lead to disease-related amyloid fibril formation.
The mechanisms of conversion of monomeric protein into condensate droplets and of the …

Intramolecular interaction kinetically regulates fibril formation by human and mouse α-synuclein

T Ohgita, H Kono, I Morita, H Oyama, T Shimanouchi… - Scientific reports, 2023 - nature.com
Regulation of α-synuclein (αS) fibril formation is a potent therapeutic strategy for αS-related
neurodegenerative disorders. αS, an intrinsically disordered 140-residue intraneural protein …

Substitution of Met-38 to Ile in γ-synuclein found in two patients with amyotrophic lateral sclerosis induces aggregation into amyloid

LD Aubrey, N Ninkina, SM Ulamec… - Proceedings of the …, 2024 - National Acad Sciences
α-, β-, and γ-Synuclein are intrinsically disordered proteins implicated in physiological
processes in the nervous system of vertebrates. α-synuclein (αSyn) is the amyloidogenic …

Mechanisms of enhanced aggregation and fibril formation of Parkinson's disease-related variants of α-synuclein

T Ohgita, N Namba, H Kono, T Shimanouchi, H Saito - Scientific reports, 2022 - nature.com
Aggregation of α-synuclein (α-syn) into amyloid fibrils is closely associated with Parkinson's
disease (PD). Familial mutations or posttranslational truncations in α-syn are known as risk …

Taking charge: metal ions accelerate amyloid aggregation in sequence variants of α-synuclein

EJ Byrd, M Wilkinson, SE Radford… - Journal of the American …, 2023 - ACS Publications
Αlpha-synuclein (αS) is an intrinsically disordered protein which exhibits a high degree of
conformational heterogeneity. In vivo, αS experiences various environments which cause …

Multifaceted interactions mediated by intrinsically disordered regions play key roles in alpha synuclein aggregation

SD Khare, P Chinchilla, J Baum - Current opinion in structural biology, 2023 - Elsevier
Abstract The aggregation of Alpha Synuclein (α-Syn) into fibrils is associated with the
pathology of several neurodegenerative diseases. Pathologic aggregates of α-Syn adopt …

Millisecond hydrogen/deuterium-exchange mass spectrometry approach to correlate local structure and aggregation in α-synuclein

N Seetaloo, M Zacharopoulou, AD Stephens… - Analytical …, 2022 - ACS Publications
In Parkinson's disease and other synucleinopathies, α-synuclein misfolds and aggregates.
Its intrinsically disordered nature, however, causes it to adopt several meta-stable …

Dissecting the self-assembly dynamics of imperfect repeats in α-Synuclein

F Huang, Y Wang, Y Zhang, C Wang… - Journal of Chemical …, 2023 - ACS Publications
The pathological aggregation of α-synuclein (αS) into amyloid fibrils is the hallmark of
Parkinson's disease (PD). The self-assembly and membrane interactions of αS are mainly …