TY  - JOUR
ID  - open3313
UR  - http://crdd.osdd.net/open/3313/
A1  - Gupta, Shalini
A1  - Ahuja, Nancy
A1  - Kumar, Sumit
A1  - Arora, Rashmi
A1  - Kumawat, Saumyata
A1  - Kaushal, Vipashu
A1  - Gupta, Pawan
Y1  - 2024/10//
N2  - 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-erb? 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-erb? 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-erb? 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-erb? 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-erb? alleviates the locomotor behavioural impairment, prevents cognitive decline and promotes motor coordination in mice. Administration of Rev-erb? 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-erb? emerges as a moonlighting nuclear receptor that could be targeted in the treatment and alleviation of Parkinson disease.
PB  - Elsevier BV
JF  - Free Radic. Biol. Med.
VL  - 223
KW  - Behaviour deficits; Differentiation; Gene regulation; Neuroprotection
TI  - Rev-erb? regulate neurogenesis through suppression of Sox2 in neuronal cells to regenerate dopaminergic neurons and abates MPP+ induced neuroinflammation
SP  - 144
EP  - 159
ER  -