Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways

Biomed Pharmacother. 2022 Sep:153:113269. doi: 10.1016/j.biopha.2022.113269. Epub 2022 Jun 18.

Abstract

In a rotenone-induced Parkinson's disease (PD) rat model, behavioral investigation, pathological examination, inflammatory factor analysis, and mitochondrial structure and function investigation verified the anti-PD efficacy of nardosinone. A combined transcriptome and proteome analysis proposed that the anti-PD target of nardosinone is the slc38a2 gene and may involve the GABAergic synaptic pathway and cAMP-signaling pathway. Analysis of targeted slc38a2 knockout cells and expression of key enzyme-encoding genes in both pathways verified the target and pathways proposed by the 'omics analysis. This further confirms that nardosinone can regulate the slc38a2 gene, a potential new target for the treatment of Parkinson's disease, and plays an anti-PD role through the GABAergic synaptic and cAMP pathways.

Keywords: GABAergic synaptic pathway; Nardosinone; Parkinson’s disease; slc38a2.

MeSH terms

  • Animals
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / genetics
  • Parkinson Disease, Secondary* / chemically induced
  • Polycyclic Sesquiterpenes
  • Rats
  • Rotenone / pharmacology

Substances

  • Polycyclic Sesquiterpenes
  • Rotenone
  • nardosinone