TY  - JOUR
AU  - Lázaro, Diana F
AU  - Amen, Triana
AU  - Gerhardt, Ellen
AU  - Song, Chengyuan
AU  - Burns, Ryan
AU  - Kruse, Niels
AU  - Santos, Patrícia I
AU  - Milovanovic, Dragomir
AU  - Höglinger, Günter
AU  - Mollenhauer, Brit
AU  - Luk, Kelvin C
AU  - Lee, Virginia My-
AU  - Outeiro, Tiago F
TI  - Synphilin-1 modulates alpha-synuclein assembly, release and uptake.
JO  - npj Parkinson's Disease
VL  - 11
IS  - 1
SN  - 2373-8057
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-01297
SP  - 326
PY  - 2025
AB  - Alpha-synuclein (aSyn) is an intrinsically disordered protein involved in phase separation and several age-associated neurodegenerative disorders, including Parkinson's disease. However, its function and pathological role remain elusive. Here, we modeled different aSyn assemblies in living cells by exploiting its interaction with synphilin-1 (Sph1). We developed a model that reports on gel- and solid-like inclusions through coexpression of aSyn and Sph1. Distinct morphological differences emerged between VN-aSyn + aSyn-VC and VN-Sph1 + aSyn-VC assemblies, showing unique antibody recognition, proteinase K resistance, and protein mobilities. The VN-Sph1 + aSyn-VC interaction could be manipulated to alter inclusion size and number. These inclusions also contained lysosomes and AP-1 vesicles, aligning with observations in human brain tissue. Our study offers new insight into aSyn aggregation and release, highlighting the importance of Sph1 and other aSyn-interacting proteins in synucleinopathies, which involve diverse copathologies only now beginning to be understood.
LB  - PUB:(DE-HGF)16
C6  - pmid:41266386
DO  - DOI:10.1038/s41531-025-01144-3
UR  - https://pub.dzne.de/record/282474
ER  -