TY  - JOUR
AU  - Tittelmeier, Jessica
AU  - Druffel-Augustin, Silke
AU  - Alik, Ania
AU  - Melki, Ronald
AU  - Nussbaum-Krammer, Carmen
TI  - Dissecting aggregation and seeding dynamics of α-Syn polymorphs using the phasor approach to FLIM.
JO  - Communications biology
VL  - 5
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - DKFZ-2022-03062
SP  - 1345
PY  - 2022
N1  - DKFZ-ZMBH Alliance / #LA:A250#
AB  - Synucleinopathies are a heterogenous group of neurodegenerative diseases characterized by the progressive accumulation of pathological α-synuclein (α-Syn). The importance of structural polymorphism of α-Syn assemblies for distinct synucleinopathies and their progression is increasingly recognized. However, the underlying mechanisms are poorly understood. Here we use fluorescence lifetime imaging microscopy (FLIM) to investigate seeded aggregation of α-Syn in a biosensor cell line. We show that conformationally distinct α-Syn polymorphs exhibit characteristic fluorescence lifetimes. FLIM further revealed that α-Syn polymorphs were differentially processed by cellular clearance pathways, yielding fibrillar species with increased seeding capacity. Thus, FLIM is not only a powerful tool to distinguish different amyloid structures, but also to monitor the dynamic process of amyloid remodeling by the cellular environment. Our data suggest that the accumulation of highly seeding competent degradation products for particular polymorphs may account for accelerated disease progression in some patients.
KW  - Humans
KW  - alpha-Synuclein: genetics
KW  - Social Group
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36477485
C2  - pmc:PMC9729209
DO  - DOI:10.1038/s42003-022-04289-6
UR  - https://inrepo02.dkfz.de/record/186273
ER  -