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Modulation of Tau Protein Neurotoxic Hallmarks by Novel σ1R Agonists/HDAC Inhibitor Dual-Acting Compounds - PubMed

3 hours ago
  • #neurodegenerative diseases
  • #dual-acting compounds
  • #tau protein
  • Study explores dual-acting compounds combining σ1R agonists and HDAC inhibitors to target tau protein neurotoxicity in Alzheimer's disease.
  • Compounds 2d and 3a showed high σ1R affinity, reduced tau aggregation and phosphorylation, and improved tau solubility.
  • Compound 2d exhibited better chemical stability and longer half-life compared to 3a.
  • In vivo tests confirmed σ1R agonist profile by reversing effects of σ1R antagonist BD-1063.
  • Dual-action approach targeting HDAC and σ1R pathways shows promise for treating tauopathies.
  • Further optimization and clinical evaluation needed for these multimodal therapies.