Version 1
: Received: 17 January 2018 / Approved: 17 January 2018 / Online: 17 January 2018 (05:26:21 CET)
How to cite:
Nishizaki, T. Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β. Preprints2018, 2018010148. https://doi.org/10.20944/preprints201801.0148.v1
Nishizaki, T. Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β. Preprints 2018, 2018010148. https://doi.org/10.20944/preprints201801.0148.v1
Nishizaki, T. Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β. Preprints2018, 2018010148. https://doi.org/10.20944/preprints201801.0148.v1
APA Style
Nishizaki, T. (2018). Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β. Preprints. https://doi.org/10.20944/preprints201801.0148.v1
Chicago/Turabian Style
Nishizaki, T. 2018 "Linoleic Acid Derivative DCP-LA Prevents Tau Phosphorylation by Targeting GSK-3β" Preprints. https://doi.org/10.20944/preprints201801.0148.v1
Abstract
Abnormal Tau phosphorylation and aggregation into neuronal paired helical filaments and neurofibrillary tangles cause tauopathies, a class of neurodegenerative diseases, that include Alzheimer’s disease, frontotemporal dementia and parkinsonism linked to chromosome 17, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration. Glycogen synthase kinase-3β (GSK-3β) is the most critical kinase to phosphorylate Tau. We have developed the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), with cyclopropane rings instead of cis-double bonds, as an anti-dementia drug. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA prevents Tau phosphorylation due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase-mediated inactivation of GSK-3β in association with PTP1B inhibition. DCP-LA targeting GSK-3β, thus, could become a valid drug for treatment of tauopathies.
Keywords
DCP-LA; PKCε; protein tyrosine phosphatase 1B; Akt; GSK-3β; tauopathy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
