Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.

ABSTRACT: Protein aggregation is a hallmark of major neurodegenerative disorders. Increasing data suggest that smaller aggregates cause higher toxic response than filamentous aggregates (fibrils). However, the size of small aggregates has challenged their detection within biologically relevant environments. Here, we report approaches to quantitatively super-resolve aggregates in live cells and ex vivo brain tissues. We show that Amytracker 630 (AT630), a commercial aggregate-activated fluorophore, has outstanding photophysical properties that enable super-resolution imaging of α-synuclein, tau, and amyloid-β aggregates, achieving ∼4 nm precision. Applying AT630 to App^NL-G-F mouse brain tissues or aggregates extracted from a Parkinson's disease donor, we demonstrate excellent agreem

SUBMITTER: Morten MJ 

PROVIDER: S-EPMC9573094 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature