Oxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson's disease.
Nutr Neurosci
; 24(3): 181-196, 2021 Mar.
Article
de En
| MEDLINE
| ID: mdl-31100053
ABSTRACT
Objectives:
Endoplasmic reticulum (ER) stress is one of the key mechanisms contributing to Parkinson's disease (PD) pathology. Pathways triggered by ER stress are protective at early stages and initiate apoptosis when the damage is extensive.Methods:
We have previously reported that oxyresveratrol rescues cells from oxidative stress and apoptosis in a cell culture model of PD. The aim of this study was to investigate whether the neuroprotective mechanism of oxyresveratrol extends to PD-associated ER stress. For this purpose, we employed two cellular models; to induce severe ER stress, Mes23.5 cells were treated with 6-hydroxydopamine (6-OHDA) and for ER stress driven by chaperones, human neuroblastoma cells were stably transfected to overexpress familial mutants of α-synuclein (α-syn).Results:
Our results indicate that oxyresveratrol exhibits distinct modes of protection in both models. In the 6-OHDA model, it inhibited the transcription of activating transcription factor 4 (ATF4), which controls the fate of pro-apoptotic proteins. On the other hand, in the α-syn model, oxyresveratrol suppressed mutant A30P oligomer formation, thereby facilitating a reduction of the ER-chaperone, 78-kDa glucose-regulated protein (Grp78).Discussion:
In summary, oxyresveratrol is protective against ER stress induced by two different triggers of PD. Owing to its wide range of defense mechanisms, oxyresveratrol is an ideal candidate for a multifactorial disease like PD.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Stilbènes
/
Extraits de plantes
/
Neuroprotecteurs
/
Syndromes parkinsoniens
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Facteur de transcription ATF-4
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Stress du réticulum endoplasmique
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Chaperonne BiP du réticulum endoplasmique
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Nutr Neurosci
Sujet du journal:
CIENCIAS DA NUTRICAO
/
NEUROLOGIA
Année:
2021
Type de document:
Article