AI Article Synopsis

  • Parkinson's Disease (PD) is characterized by neuroinflammation, and the nuclear receptor NR1H4 is found to play a role in regulating inflammation in the central nervous system.
  • Research using various molecular techniques revealed that NR1H4 expression decreases during PD progression, and manipulating its levels affects astrocyte activation and inflammatory responses.
  • Activating NR1H4 with Obeticholic acid showed promise in reducing neuroinflammation and promoting neuron survival, highlighting its potential neuroprotective effects against PD.

Article Abstract

Parkinson's Disease (PD) is a degenerative disease driven by neuroinflammation. Nuclear receptor subfamily 1 group H member 4 (NR1H4), a nuclear receptor involved in metabolic and inflammatory regulation, is found to be widely expressed in central nervous system. Previous studies suggested the protective role of NR1H4 in various diseases related to inflammation, whether NR1H4 participates in PD progression remains unknown. To investigate the role of NR1H4 in neuroinflammation regulation, especially astrocyte activation during PD, siRNA and adenovirus were used to manipulate Nr1h4 expression. RNA-sequencing (RNA-seq), quantitative real-time PCR, enzyme-linked immunosorbent assay, Chromatin immunoprecipitation and western blotting were performed to further study the underlying mechanisms. We identified that NR1H4 was down-regulated during PD progression. In vitro experiments suggested that Nr1h4 knockdown led to inflammatory response, reactive oxygen species generation and astrocytes activation whereasNr1h4 overexpressionhad the opposite effects. The results of RNA-seq on astrocytes revealed that NR1H4 manipulated neuroinflammation in a CEBPβ/NF-κB dependent manner. Additionally, pharmacological activation of NR1H4 via Obeticholic acid ameliorated neuroinflammation and promoted neuronal survival. Our study first proved the neuroprotective effects of NR1H4against PD via inhibiting astrocyte activation and neuroinflammation in a CEBPβ/NF-κB dependent manner.

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Source
http://dx.doi.org/10.1016/j.intimp.2024.113087DOI Listing

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