NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes

Show full item record



Permalink

http://hdl.handle.net/10138/310652

Citation

Oksanen , M , Hyötyläinen , I , Trontti , K , Rolova , T , Wojciechowski , S , Koskuvi , M , Viitanen , M , Levonen , A-L , Hovatta , I , Roybon , L , Lehtonen , S , Kanninen , K M , Hämäläinen , R H & Koistinaho , J 2020 , ' NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes ' , Glia , vol. 68 , no. 3 , pp. 589-599 . https://doi.org/10.1002/glia.23741

Title: NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes
Author: Oksanen, Minna; Hyötyläinen, Ida; Trontti, Kalevi; Rolova, Taisia; Wojciechowski, Sara; Koskuvi, Marja; Viitanen, Matti; Levonen, Anna-Liisa; Hovatta, Iiris; Roybon, Laurent; Lehtonen, Sarka; Kanninen, Katja M.; Hämäläinen, Riikka H.; Koistinaho, Jari
Contributor: University of Helsinki, SLEEPWELL Research Program
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2020-03
Language: eng
Number of pages: 11
Belongs to series: Glia
ISSN: 0894-1491
URI: http://hdl.handle.net/10138/310652
Abstract: Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.
Subject: Alzheimer's disease
astrocytes
inflammation
NRF2
oxidative stress
REMITTING MULTIPLE-SCLEROSIS
RELEASE DIMETHYL FUMARATE
OXIDATIVE STRESS
INTEGRATED ANALYSIS
MOUSE MODEL
GLUTATHIONE
NEURONS
NEUROINFLAMMATION
REGULATORS
3112 Neurosciences
3124 Neurology and psychiatry
515 Psychology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Oksanen_et_al_2020_Glia.pdf 3.047Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record