{"title":"Rev-erbα通过抑制神经元细胞中的Sox2来调节神经发生,从而再生多巴胺能神经元,并减轻MPP+诱导的神经炎症。","authors":"","doi":"10.1016/j.freeradbiomed.2024.07.025","DOIUrl":null,"url":null,"abstract":"<div><p>Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos.</p><p>The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal <em>in vitro</em> model of Parkinson's disease.</p><p>Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an <em>in vitro</em> and <em>in vivo</em> Parkinson's disease model.</p><p>We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.</p></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation\",\"authors\":\"\",\"doi\":\"10.1016/j.freeradbiomed.2024.07.025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos.</p><p>The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal <em>in vitro</em> model of Parkinson's disease.</p><p>Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an <em>in vitro</em> and <em>in vivo</em> Parkinson's disease model.</p><p>We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.</p></div>\",\"PeriodicalId\":12407,\"journal\":{\"name\":\"Free Radical Biology and Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Free Radical Biology and Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0891584924005719\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Free Radical Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891584924005719","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation
Parkinson's disease is a progressive neurodegenerative disease that affects the motor and non-motor circuits of the brain. Currently, there are no promising therapeutic measures for Parkinson's disease, and most strategies designed to alleviate the Parkinson's disease are palliative. The dearth of therapeutic interventions in Parkinson's disease has driven attention in the search for targets that may augment dopamine secretion, promote differentiation towards dopaminergic neuronal lineage, or aid in neuroprotection from neuronal stress and inflammation, and prevent Parkinson's disease associated motor impairment and behavioural chaos.
The study first reports that Rev-erbα plays an important role in regulating the differentiation of undifferentiated neuronal cells towards dopaminergic neurons through abating Sox2 expression in human SH-SY5Y cells. Rev-erbα directly binds to the human Sox2 promoter region and represses their expression to promote differentiation towards dopaminergic neurons. We have reported a novel mechanism of Rev-erbα which effectively abrogates 1-methyl-4-phenylpyridinium induced cytotoxicity, inflammation, and oxidative stress, exerted a beneficial effect on transmembrane potential, and suppressed apoptosis in the neuronal in vitro model of Parkinson's disease.
Rev-erbα ligand SR9011 was observed to ease the disease severity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mouse model of Parkinson's disease. Rev-erbα alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erbα ligand also helps in replenishing the dopaminergic neurons and abrogating the neurotoxin mediated toxicity in an in vitro and in vivo Parkinson's disease model.
We conclude that Rev-erbα emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.
期刊介绍:
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.