TY  - JOUR
AU  - Pesch, Verena
AU  - Flores-Fernandez, José Miguel
AU  - Reithofer, Sara
AU  - Ma, Liang
AU  - Özdüzenciler, Pelin
AU  - Busch, Yannick
AU  - Sriraman, Aishwarya
AU  - Wang, YongLiang
AU  - Amidian, Sara
AU  - Kroepel, Chiara V M
AU  - Müller, Laura
AU  - Lien, Yi
AU  - Rudtke, Olivia
AU  - Frieg, Benedikt
AU  - Schröder, Gunnar F
AU  - Wille, Holger
AU  - Tamgüney, Gültekin
TI  - Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson’s disease
JO  - Brain
VL  - 147
IS  - 5
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - FZJ-2024-03241
SP  - 1644-1652
PY  - 2024
AB  - The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/- mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders.
LB  - PUB:(DE-HGF)16
C6  - 38428032
UR  - <Go to ISI:>//WOS:001206420100001
DO  - DOI:10.1093/brain/awae061
UR  - https://juser.fz-juelich.de/record/1025963
ER  -