RT Journal Article
T1 Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment
A1 Moyano-Cires Ivanoff, Paula Viviana
A1 Flores, Andrea
A1 Sanjuan, Javier
A1 Plaza Hernández, José Carlos
A1 Guerra Menéndez, Lucía
A1 Abascal, Luisa
A1 Mateo Sierra, Olga
A1 Pino Sans, Javier Del
AB Butylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN loss, we employed BF SN56 cholinergic wild-type or silenced cells for Tau, amyloid-beta precursor protein (βApp), acetylcholinesterase (AChE), or glycogen synthase kinase-3 beta (GSK3β) genes, exposing them to BP (0.1-80 µM) for 1 or 14 days alongside triiodothyronine (T3; 15 nM), N-acetylcysteine (NAC; 1 mM), or recombinant heat shock protein 70 (rHSP70; 30 µM). BP disrupted cholinergic transmission by AChE inhibition and provoked cell death through thyroid hormones (THs) pathway disruption, Aβ/p-Tau protein accumulation, AChE-S overexpression, and oxidative stress (OS). Aβ/p-Tau accumulation was correlated with HSP70 downregulation, OS exacerbation, and GSK3β hyperactivation (for p-Tau). BP-induced OS was mediated by reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (NRF2) pathway disruption. All observed effects were contingent upon TH signaling impairment. These findings uncover novel mechanistic links between BP exposure and BFCN neurodegeneration, providing a framework for therapeutic strategies
PB MDPI
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/125963
UL https://hdl.handle.net/20.500.14352/125963
LA eng
NO Moyano, P., Flores, A., Sanjuan, J., Plaza, J. C., Guerra-Menéndez, L., Abascal, L., Mateo, O., & Del Pino, J. (2025). Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment. Biology, 14(10), 1380. https://doi.org/10.3390/biology14101380
NO Author Contributions: Conceptualization, J.d.P., P.M. and A.F.; methodology, J.d.P., P.M., A.F. and J.S.; software, J.d.P., P.M. and A.F.; validation, J.d.P. and P.M.; formal analysis, A.F.; investigation, A.F., L.G.-M., O.M., J.C.P. and J.S.; data curation, J.d.P., P.M. and J.S.; writing—original draft preparation, J.d.P., P.M., A.F., J.C.P., O.M. and L.G.-M.; writing—review and editing, A.F., J.d.P., P.M., J.S., L.G.-M., J.C.P., L.A. and O.M.; visualization, L.G.-M.; supervision, J.d.P., P.M. and A.F.; project administration, J.d.P. and P.M.; funding acquisition, J.d.P. and P.M. All authors have read and agreed to the published version of the manuscript.
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 31 dic 2025