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primary topic: Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation

Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation
type: AcademicArticle
type: Article
abstract: 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.
date: 2024-10
volume: 223
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository

Elsevier BV
type: Organization

Free Radic. Biol. Med.
type: Collection

Nancy Ahuja
type: Person
given name: Nancy
family name: Ahuja

Sumit Kumar
type: Person
given name: Sumit
family name: Kumar

Pawan Gupta
type: Person
given name: Pawan
family name: Gupta

Saumyata Kumawat
type: Person
given name: Saumyata
family name: Kumawat

Rashmi Arora
type: Person
given name: Rashmi
family name: Arora

Vipashu Kaushal
type: Person
given name: Vipashu
family name: Kaushal

Shalini Gupta
type: Person
given name: Shalini
family name: Gupta

HTML Summary of #3313 Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation
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primary topic: Rev-erbα regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation