creators_name: Ahuja, Nancy
creators_name: Gupta, Shalini
creators_name: Arora, Rashmi
creators_name: Bhagyaraj, Ella
creators_name: Tiwari, Drishti
creators_name: Kumar, Sumit
creators_name: Gupta, Pawan
type: article
datestamp: 2024-06-25 01:54:56
lastmod: 2024-06-25 01:54:56
metadata_visibility: show
title: Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson ` s
ispublished: pub
subjects: QR
note: The copyright of this article belongs to ROCKFELLER UNIVERSITY PRESS
abstract: 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.
date: 2024-07
date_type: published
publication: LIFE SCIENCE ALLIANCE
volume: 7
number: 7
publisher: ROCKFELLER UNIVERSITY PRESS
id_number: 10.26508/lsa.202302416
refereed: TRUE
official_url: https://www.life-science-alliance.org/content/7/7/e202302416
citation:   Ahuja, Nancy and Gupta, Shalini and Arora, Rashmi and Bhagyaraj, Ella and Tiwari, Drishti and Kumar, Sumit and Gupta, Pawan  (2024) Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson ` s.  LIFE SCIENCE ALLIANCE, 7 (7).