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

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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.

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Data Availability

The datasets supporting the conclusions of this article are included within the article.

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Funding

The National Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0099).

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Author notes

  1. Na Zhao and Tingting Wang have equally contributed to the work.

Authors and Affiliations

  1. Department of Pathology, Basic Medical College, Chongqing Medical University, Yixueyuan Road 1, Chongqing, 400016, People’s Republic of China

    Na Zhao, Tingting Wang, Li Peng, Yumei Li, Yong Zhao & Shanshan Yu

  2. Molecular Medical Laboratory, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Na Zhao, Tingting Wang, Li Peng, Yumei Li, Yong Zhao & Shanshan Yu

  3. Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Na Zhao, Tingting Wang, Li Peng, Yumei Li, Yong Zhao & Shanshan Yu

  4. Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Na Zhao, Tingting Wang, Li Peng, Yumei Li, Yong Zhao & Shanshan Yu

Authors
  1. Na Zhao
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  2. Tingting Wang
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  3. Li Peng
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  4. Yumei Li
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Contributions

NA, TW and SY designed the experiments. NA, TW, LP and YL contributed to the execution of the entire experiments, NA and TW performed the statistical analysis. NA, TW and SY drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shanshan Yu.

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The authors declare that they have no conflict of interest.

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All experiments were authorized by the Institutional Animal Ethics Committee of Chongqing Medical University, Chongqing, China, and procedures were performed in compliance with the Guide for the Care and Use of Laboratory Animals. Maximum efforts were made to minimize animal suffering. Ethical Code Number: 2020011.

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Zhao, N., Wang, T., Peng, L. et al. Attenuation of Inflammation by DJ-1 May Be a Drug Target for Cerebral Ischemia–Reperfusion Injury. Neurochem Res 46, 1470–1479 (2021). https://doi.org/10.1007/s11064-021-03288-z

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  • DOI: https://doi.org/10.1007/s11064-021-03288-z

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