Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons.

Autor:	Leow DM; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore., Cheah IK; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Chen L; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore., Ng YK; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore., Yeo CJ; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore.; National Neuroscience Institute (NNI), Singapore 308433, Singapore.; Institute of Education in Healthcare and Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen AB51 7HA, UK.; Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Department of Neurology, Feinberg School of Medicine, Northwestern University, Evanston, IL 60611, USA.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore., Halliwell B; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore., Ong WY; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.; Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Jazyk:	angličtina
Zdroj:	Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2024 Jun 05; Vol. 13 (6). Date of Electronic Publication: 2024 Jun 05.
DOI:	10.3390/antiox13060693
Abstrakt:	Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson's disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA-treated human neuroblastoma SH-SY5Y cells. In 6-OHDA-treated cells, decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels were observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly decreased when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter OCTN1 abrogated ET's cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson's disease.
Databáze:	MEDLINE
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