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Article: Oxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson’s disease

TitleOxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson’s disease
Authors
Keywordsα-synuclein
ER stress oxyresveratrol
Parkinson’s disease
6-OHDA
Issue Date2021
PublisherTaylor & Francis. The Journal's web site is located at http://www.tandfonline.com/loi/ynns20
Citation
Nutritional Neuroscience, 2021, v. 24 n.3, p. 181-196 How to Cite?
AbstractObjectives: 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.
Persistent Identifierhttp://hdl.handle.net/10722/276232
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 0.887
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSHAH, A-
dc.contributor.authorChao, J-
dc.contributor.authorLegido-Quigley, C-
dc.contributor.authorChang, RCC-
dc.date.accessioned2019-09-10T02:58:41Z-
dc.date.available2019-09-10T02:58:41Z-
dc.date.issued2021-
dc.identifier.citationNutritional Neuroscience, 2021, v. 24 n.3, p. 181-196-
dc.identifier.issn1028-415X-
dc.identifier.urihttp://hdl.handle.net/10722/276232-
dc.description.abstractObjectives: 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.-
dc.languageeng-
dc.publisherTaylor & Francis. The Journal's web site is located at http://www.tandfonline.com/loi/ynns20-
dc.relation.ispartofNutritional Neuroscience-
dc.rightsAOM/Preprint Before Accepted: his article has been accepted for publication in [JOURNAL TITLE], published by Taylor & Francis. AOM/Preprint After Accepted: This is an [original manuscript / preprint] of an article published by Taylor & Francis in [JOURNAL TITLE] on [date of publication], available online: http://www.tandfonline.com/[Article DOI]. Accepted Manuscript (AM) i.e. Postprint This is an Accepted Manuscript of an article published by Taylor & Francis in [JOURNAL TITLE] on [date of publication], available online: http://www.tandfonline.com/[Article DOI].-
dc.subjectα-synuclein-
dc.subjectER stress oxyresveratrol-
dc.subjectParkinson’s disease-
dc.subject6-OHDA-
dc.titleOxyresveratrol exerts ATF4- and Grp78-mediated neuroprotection against endoplasmic reticulum stress in experimental Parkinson’s disease-
dc.typeArticle-
dc.identifier.emailChang, RCC: rccchang@hku.hk-
dc.identifier.authorityChang, RCC=rp00470-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1080/1028415X.2019.1613764-
dc.identifier.scopuseid_2-s2.0-85066072913-
dc.identifier.hkuros303971-
dc.identifier.hkuros328438-
dc.identifier.volume24-
dc.identifier.issue3-
dc.identifier.spage181-
dc.identifier.epage196-
dc.identifier.isiWOS:000470479200001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1028-415X-

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