TY  - JOUR
KW  - Animals
KW  -  Humans
KW  -  Mice
KW  -  Alzheimer Disease
KW  -  Amyloid beta-Peptides
KW  -  Calcium
KW  -  Calcium Channels
KW  -  Calcium Signaling
KW  -  Cytoskeleton
KW  -  Disease Models
KW  -  Animal
KW  -  Homeostasis
KW  -  Neuronal Plasticity
KW  -  Neuroprotective Agents
KW  -  Septins
KW  -  tau Proteins
TI  - Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease
UR  - https://doi.org/10.1126/science.add6260
AV  - public
JF  - Science
SN  - 0036-8075
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10193867
PB  - American Association for the Advancement of Science (AAAS)
A1  - Princen, Katrien
A1  - Van Dooren, Tom
A1  - van Gorsel, Marit
A1  - Louros, Nikolaos
A1  - Yang, Xiaojuan
A1  - Dumbacher, Michael
A1  - Bastiaens, Ilse
A1  - Coupet, Kristel
A1  - Dupont, Shana
A1  - Cuveliers, Eva
A1  - Lauwers, Annick
A1  - Laghmouchi, Mohamed
A1  - Vanwelden, Thomas
A1  - Carmans, Sofie
A1  - Van Damme, Nele
A1  - Duhamel, Hein
A1  - Vansteenkiste, Seppe
A1  - Prerad, Jovan
A1  - Pipeleers, Karolien
A1  - Rodiers, Olivier
A1  - De Ridder, Liese
A1  - Claes, Sofie
A1  - Busschots, Yoni
A1  - Pringels, Lentel
A1  - Verhelst, Vanessa
A1  - Debroux, Eveline
A1  - Brouwer, Marinka
A1  - Lievens, Sam
A1  - Tavernier, Jan
A1  - Farinelli, Melissa
A1  - Hughes-Asceri, Sandrine
A1  - Voets, Marieke
A1  - Winderickx, Joris
A1  - Wera, Stefaan
A1  - de Wit, Joris
A1  - Schymkowitz, Joost
A1  - Rousseau, Frederic
A1  - Zetterberg, Henrik
A1  - Cummings, Jeffrey L
A1  - Annaert, Wim
A1  - Cornelissen, Tom
A1  - De Winter, Hans
A1  - De Witte, Koen
A1  - Fivaz, Marc
A1  - Griffioen, Gerard
VL  - 384
Y1  - 2024/05/31/
N2  - Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-? and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-? and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments.
IS  - 6699
ER  -