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Hippocampal Hap1 downregulation exacerbates Alzheimer's disease-related neuropathology through impairment of glucocorticoid receptor nuclear translocation in APP/PS1 mice - PubMed

4 days ago
  • #Alzheimer's disease
  • #Glucocorticoid receptor
  • #Synaptic plasticity
  • Hippocampal Hap1 downregulation worsens Alzheimer's disease (AD) neuropathology in APP/PS1 mice.
  • Hap1 regulates glucocorticoid receptor (GR) nuclear translocation in the hippocampus.
  • Hap1 expression decreases with aging and AD progression in APP/PS1 mice.
  • Hap1 knockdown leads to cognitive deficits, synaptic loss, and increased Aβ deposition.
  • Hap1 deficiency disrupts GR nuclear translocation and BDNF transcription.
  • Hap1 knockdown elevates corticosterone levels and causes depressive-like behaviors.
  • Hap1-mediated GR nuclear translocation is a key mechanism in AD synaptic failure.
  • Hap1 modulation is suggested as a potential therapeutic target for AD.