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HM568 Enhances NAD+ Biosynthesis to Ameliorate Mitochondrial Dysfunction and Neurotoxicity in Parkinson's Disease Models: A Putative Link to PARP1 Modulation - PubMed

3 hours ago
  • #Parkinson's Disease
  • #NAD+ Biosynthesis
  • #Mitochondrial Dysfunction
  • HM568 improves behavioral deficits, prevents dopaminergic neuron loss, and restores blood-brain barrier integrity and mitochondrial morphology in Parkinson's disease models.
  • HM568 counteracts MPP+-induced inhibition of mitochondrial respiratory chain complexes I, III, and IV, restoring mitochondrial function.
  • HM568 elevates intracellular NAD+ levels, downregulates PARP1 protein expression, and inhibits its enzymatic activity.
  • Molecular docking and dynamics simulations show HM568 has high binding affinity and selective inhibition for PARP1 over PARP2.
  • HM568 may correct mitochondrial dysfunction and energy imbalance via PARP1 inhibition and NAD+ metabolism modulation, suggesting therapeutic potential for Parkinson's disease.