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Neuroprotective effect of astrocytic dopamine Drd2 receptor on mitochondrial complex I in a mouse model of Parkinson's disease through β-arrestin2-NDUFA10 regulation - PubMed

4 hours ago
  • #Parkinson's disease
  • #astrocytic D2 receptor
  • #mitochondrial complex I
  • The study reveals the neuroprotective role of astrocytic dopamine D2 (Drd2) receptors in Parkinson's disease (PD) by improving mitochondrial function in a mouse model.
  • Deletion of astrocytic Drd2 receptors worsens mitochondrial dysfunction, as shown by transcriptome sequencing and metabolomics.
  • Mechanistically, Drd2 activation recruits β-arrestin2 to regulate mitochondrial complex I activity by interacting with subunits NDUFA4 and NDUFA10.
  • Knockdown of NDUFA10 in astrocytes abolishes the neuroprotective effects of Drd2 activation, highlighting its critical role.
  • The findings provide a new framework for developing combination therapies targeting mitochondrial dysfunction and dopamine receptor dysregulation in PD.