PADI4 mediates autophagy and participates in the role of ganoderic acid A monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway

Biosci Biotechnol Biochem. 2021 Jul 23;85(8):1818-1829. doi: 10.1093/bbb/zbab054.

Abstract

The effects of PADI4 and GAA on the senescence of Alzheimer's cells were explored in the present work. HT22 cells were treated with Aβ25-35 to establish an Alzheimer's model and were then treated with different concentrations of GAA and transfected with a siPADI4 lentiviral vector. GAA could reverse the effects of Aβ25-35 on inhibiting cell viability and promoting apoptosis and senescence. siPADI4 reduced Aβ25-35-induced cell viability and upregulated Aβ25-35-induced cell apoptosis and senescence, as well as partially reversed the effect of GAA on cells, and these results were confirmed by detecting the expressions of senescence- and apoptosis-related proteins. In addition, siPADI4 was found to promote the phosphorylation of Akt and mTOR, which was partially reversed by GAA. In conclusion, PADI4 mediates autophagy and participates in the role of GAA monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway.

Keywords: Akt/mTOR pathway; Alzheimer's disease; PADI4; ganoderic acid A; senescence.

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Autophagy / physiology*
  • Cell Line
  • Cellular Senescence / drug effects*
  • Heptanoic Acids / chemistry
  • Heptanoic Acids / pharmacology*
  • Humans
  • Lanosterol / analogs & derivatives*
  • Lanosterol / chemistry
  • Lanosterol / pharmacology
  • Protein-Arginine Deiminase Type 4 / physiology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Heptanoic Acids
  • Lanosterol
  • ganoderic acid A
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4