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@ARTICLE{Lzaro:282474,
author = {Lázaro, Diana F and Amen, Triana and Gerhardt, Ellen and
Song, Chengyuan and Burns, Ryan and Kruse, Niels and Santos,
Patrícia I and Milovanovic, Dragomir and Höglinger,
Günter and Mollenhauer, Brit and Luk, Kelvin C and Lee,
Virginia My- and Outeiro, Tiago F},
title = {{S}ynphilin-1 modulates alpha-synuclein assembly, release
and uptake.},
journal = {npj Parkinson's Disease},
volume = {11},
number = {1},
issn = {2373-8057},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-01297},
pages = {326},
year = {2025},
abstract = {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.},
cin = {AG Fischer / AG Milovanovic (Berlin) / Clinical Research
(Munich)},
ddc = {610},
cid = {I:(DE-2719)1410002 / I:(DE-2719)1813002 /
I:(DE-2719)1111015},
pnm = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351) / 353 - Clinical and Health Care Research
(POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351 /
G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41266386},
doi = {10.1038/s41531-025-01144-3},
url = {https://pub.dzne.de/record/282474},
}