Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting

Mahmoudian Esfahani, Maryam; Mostashfi, Maryam; Vaheb Hosseinabadi, Shiva; Hashemi, Motahare-Sadat; Peymani, Maryam; Zohrabi, Dina; Angaji, Seyed Abdolhamid; Nasr-Esfahani, Mohammad Hossein; Ghaedi, Kamran

doi:10.1016/j.neures.2023.12.001

Cited by 1 publication

(1 citation statement)

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“…We first looked for the expression of Nr1h4 and Thrb upon MPP + exposure where we found the increased expression of both these receptors at mRNA and protein levels ( Fig 4A ). We used a 500 μM MPP + concentration as it is the lowest concentration that decreased the cell viability significantly as observed by us and reported by other groups ( Mazzio & Soliman, 2012 ; Su et al, 2021 ; Mahmoudian Esfahani et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson’s

Ahuja,

Gupta,

Arora

et al. 2024

Life Sci. Alliance

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Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes. A combination of both ligands is effective in mitigating cell death induced by TM. Further exploration of their protective effects in the Parkinson’s disease (PD) model shows that they reduce MPP+-induced dissipation of mitochondrial membrane potential and ROS generation in an in vitro PD model in neuronal cells. Furthermore, the generation of an experimental murine PD model reveals that simultaneous treatment of GW4064 and T3 protects mice from ER stress, dopaminergic cell death, and functional deficits in the MPTP mouse model of PD. Thus, activation of Nr1h4 and Thrb by their respective ligands plays an indispensable role in ER stress amelioration and mounts protective effects in the MPTP mouse model of PD.

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Section: Resultsmentioning

confidence: 99%