Journal Article

FZJ-2026-04734

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png α‐Synuclein Aggregate‐Disassembling Compounds Prolong Survival in a Mouse Model of Parkinson's Disease

Reithofer, S. ; Sevenich, M. ; Vollmer, M. ; Kurtul, D. ; Müller, L. ; Özdüzenciler, P.FZJ* ; Gerhards, L.FZJ* ; Allmeroth, K. ; Wendt, M. ; Charbgoo, F. ; Schemmert, S. ; Naumann, M. ; Korostov, K. ; Hartmann, G. ; Gremer, L.FZJ* ; Tamgüney, G. (Corresponding author)FZJ* ; Willbold, D. ; Willuweit, A.FZJ*

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/agt2.70439

Abstract: Pathological aggregation of α-synuclein drives neuronal loss in Parkinson’s disease. We therefore tested two optimized all- d - peptides, SVD-17 and SVD-1a, alongside the prototype SVD-1. Surface plasmon resonance revealed that SVD-17 binds monomeric α-synuclein with a nanomolar KD of 1.09 nM. In vitro, SVD-17 and SVD-1a dismantled existing fibrils, rendering 50 % of them seeding-incompetent at 1.4 μM and 5.1 μM, respectively, and suppressed seeded aggregation in HEK293 α-synuclein biosensor cells with an IC50 of 1.6 μM. Hemizygous TgM83+ / − mice received continuous subcutaneous infusion of each peptide for 3 months following intraperitoneal fibril seeding and were then monitored for neurological decline. Treatment with SVD-17 or SVD-1a extended median survival by 14% and 15%, whereas SVD-1 provided no significant benefit. Collectively, SVD-17 and SVD-1a bind α-synuclein with high affinity, disaggregate pathogenic assemblies, block further polymerization, and improve outcomes in a stringent in vivo model, underscoring their potential as disease-modifying therapeutics for Parkinson’s disease and other synucleinopathies.

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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 2026

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Database coverage:
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