% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Fischer:277807,
author = {Fischer, Anna-Lisa and Schmitz, Matthias and Thom, Tobias
and Zafar, Saima and Younas, Neelam and da Silva Correia,
Susana and Silva-Correia, Susana and Canaslan, Sezgi and
Zerr, Inga},
title = {{A}lpha-{S}ynuclein {D}emonstrates {V}arying {B}inding
{A}ffinities {W}ith {D}ifferent {T}au {I}soforms.},
journal = {Journal of neurochemistry},
volume = {169},
number = {4},
issn = {0022-3042},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2025-00479},
pages = {e70053},
year = {2025},
abstract = {The hallmark of various neurodegenerative diseases is the
accumulation and aggregation of amyloidogenic proteins, such
as amyloid-beta (Aβ) and tau in Alzheimer's disease (AD)
and alpha-synuclein (aSyn) in synucleinopathies. Many
neurodegenerative diseases express mixed pathology. For
instance, Lewy bodies are reported in tauopathies and
neurofibrillary tau-tangles are detected in
synucleinopathies, suggesting a potential co-existence or
crosstalk of misfolded aSyn and tau. In the present study,
we investigated the binding characteristics of monomeric
aSyn with different tau isoforms by using surface plasmon
resonance (SPR) spectroscopy allowing monitoring direct
protein-protein interactions and their potential
co-localization using SH-SY5Y cells. The calculation of the
binding parameters (association and dissociation rate
constants) indicated the strongest binding affinity between
aSyn and tau isoform 1N3R followed by tau 2N3R and tau 2N4R.
Co-localization studies in SH-SY5Y cells, treated with aSyn
and all six tau isoforms revealed an intracellular
co-localization of aSyn with different isoforms of tau.
Subcellular fractionation confirmed the cellular uptake and
colocalization of tau and aSyn in the same compartment,
showing their expression in membrane, nuclear, and
cytoskeletal fractions. Understanding the intricate
interplay between aSyn and tau is crucial for unraveling the
pathophysiology of PD, AD, and related neurodegenerative
disorders, ultimately paving the way for the development of
effective treatments targeting this interaction. In
conclusion, our data indicate that aSyn and tau are direct
interaction partners with varying binding affinities
depending on the tau isoform. This interaction may be
significant for understanding the pathophysiology of
dementia with mixed pathologies.},
keywords = {Humans / tau Proteins: metabolism / alpha-Synuclein:
metabolism / Protein Isoforms: metabolism / Protein Binding:
physiology / Cell Line, Tumor / Surface Plasmon Resonance /
Alzheimer's disease (Other) / Parkinson's disease (Other) /
alpha‐synuclein (Other) / interaction (Other) /
synucleinopathies (Other) / tau (Other) / tauopathies
(Other) / tau Proteins (NLM Chemicals) / alpha-Synuclein
(NLM Chemicals) / Protein Isoforms (NLM Chemicals)},
cin = {AG Zerr},
ddc = {610},
cid = {I:(DE-2719)1440011-1},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40165586},
doi = {10.1111/jnc.70053},
url = {https://pub.dzne.de/record/277807},
}