RT Journal Article
T1 The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
A1 Alonso, Eva
A1 Vale González, María del Carmen
A1 Rodríguez Vieytes, Mercedes
A1 Laferla, Frank M.
A1 Giménez-Llort, Lydia
A1 Botana López, Luis Miguel
K1 Gymnodimine
K1 Alzheimer disease
K1 Tau protein
K1 Beta-amyloid
K1 Acetylcholine
AB Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.
PB Karger
SN 1015-8987
YR 2011
FD 2011-06-17
LK https://hdl.handle.net/10347/47339
UL https://hdl.handle.net/10347/47339
LA eng
NO Eva Alonso, Carmen Vale, Mercedes R. Vieytes, Frank M. Laferla, Lydia Giménez-Llort, Luis M. Botana; The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an in Vitro Model of Alzheimer Disease. Cellular Physiology and Biochemistry 1 June 2011; 27 (6): 783–794. https://doi.org/10.1159/000330086
NO This is the peer-reviewed but unedited manuscript version of the following article: Eva Alonso, Carmen Vale, Mercedes R. Vieytes, Frank M. Laferla, Lydia Giménez-Llort, Luis M. Botana; The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an in Vitro Model of Alzheimer Disease. Cellular Physiology and Biochemistry 1 June 2011; 27 (6): 783–794. The final, published version is available at https://doi.org/10.1159/000330086
NO This work was funded with the following FEDER cofunded-grants:  SAF2009-12581 (subprograma NEF), AGL2009-13581-CO2-01, TRA2009-0189, AGL2010-17875. From Xunta de Galicia, Spain: GRC 2010/10, and PGIDT07CSA012261PR, PGDIT 07MMA006261PR, PGIDIT (INCITE) 09MMA003261PR, 2009/XA044, 2009/053 (Consell. Educación), 2008/CP389  (EPITOX, Consell. Innovación e Industria, programa IN.CI.TE.), 10PXIB261254 PR. From  EU VIIth Frame Program: 211326 - CP (CONffIDENCE), 265896 BAMMBO,  265409 µAQUA, and 262649 BEADS. From the Atlantic Area Programme  (Interreg IVB Trans-national): 2008-1/003 (Atlantox) and 2009-1/117  Pharmatlantic. Eva Alonso is recipient of a predoctoral fellowship from Fondo de Investigaciones Sanitarias (pFIS), Ministerio de Sanidad y Consumo, Spain.
DS Minerva
RD 22 may 2026