Attenuation of Inflammation by DJ-1 May Be a Drug Target for Cerebral Ischemia-Reperfusion Injury

Neurochem Res. 2021 Jun;46(6):1470-1479. doi: 10.1007/s11064-021-03288-z. Epub 2021 Mar 8.

Abstract

The pathophysiological process of cerebral apoplexy is complex, and there are currently no specific drugs for this condition. The study of effective drug targets has become a hot topic in neuroscience. Currently, adeno-associated viruses (AAVs) and polypeptides are commonly used in drug research. DJ-1 has been widely considered a neuroprotective target in recent times, but the mechanism of its neuroprotective effects is unclear. In this study, we simulated ischemic injury by establishing a middle cerebral artery occlusion reperfusion (MCAO/R) model to compare the protective effect of DJ-1 overexpression induced by DJ-1 AAV and ND-13 on cerebral ischemia-reperfusion (I/R) injury. We found that DJ-1 overexpression and ND-13 significantly reduced the neurological function scores and infarct volume and alleviated pathological damage to brain tissue. In addition, Western blotting, ELISA and immunofluorescence labeling revealed that DJ-1 overexpression and ND-13 increased the expression of the anti-inflammatory cytokines IL-10 and IL-4, and decreased the levels of the pro-inflammatory cytokines IL-1β and TNF-α. In summary, our study shows that DJ-1 overexpression and ND-13 can regulate the expression of inflammatory factors and alleviate cerebral I/R injury. Thus, DJ-1 is a possible drug target for cerebral I/R injury.

Keywords: Adeno-associated viruses; DJ-1; Ischemia–reperfusion; ND-13; Neuroprotection.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Cytokines / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Neuroprotective Agents / therapeutic use*
  • Peptide Fragments / therapeutic use*
  • Protein Deglycase DJ-1 / metabolism*
  • Protein Deglycase DJ-1 / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology

Substances

  • Cytokines
  • DJ-1 based peptide, ND-13
  • Neuroprotective Agents
  • Peptide Fragments
  • PARK7 protein, rat
  • Protein Deglycase DJ-1