Journal Article

FZJ-2024-03241

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson’s disease

Pesch, V. ; Flores-Fernandez, J. M. ; Reithofer, S.FZJ* ; Ma, L.FZJ* ; Özdüzenciler, P.FZJ* ; Busch, Y. ; Sriraman, A. ; Wang, Y. ; Amidian, S. ; Kroepel, C. V. M.FZJ* ; Müller, L. ; Lien, Y. ; Rudtke, O. ; Frieg, B. ; Schröder, G. F.FZJ* ; Wille, H. (Corresponding author) ; Tamgüney, G. (Corresponding author)FZJ*

2024
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awae061  doi:10.34734/FZJ-2024-03241

Abstract: 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.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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