Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3301-3310.doi: 10.4103/NRR.NRR-D-25-00293

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Delta-opioid receptor–mediated neural protection and regeneration

Jiahui Li1, 2, Yuan Xu3, 4, Ziyu Chao1, 2, Leena Khiati5, Ying Xia1, 2, *   

  1. 1Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai, China; 
    2Shanghai Research Center for Acupuncture and Meridians, Shanghai, China; 
    3Department of Neurosurgery, The First People’s Hospital of Changzhou, Changzhou, Jiangsu Province, China; 
    4Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China; 
    5Dubai Medical University, College of Medicine, Dubai, The United Arab Emirates
  • Online:2026-08-18 Published:2026-04-23
  • Contact: Ying Xia, MD, PhD, Y55738088@gmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81873361 (to YXia), 82101533 (to YXu); a grant from Science and Technology Commission of Shanghai Municipality, No. 18401970100 (to YXia); Top Talent of Changzhou “The 14th Five-Year Plan” High-Level Health Talents Training Project, No.2022CZBJ047 (to YXu); Young Talent Development Plan Project of Changzhou Health Commission, No. CZQM2020043 (to YXu).

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Abstract: The delta-opioid receptor was previously viewed as a mediator in pain regulation. Recent data shed light on its specific role in neural protection and regeneration. An up-regulation of delta-opioid receptor expression and/or activity protects neuronal cells/tissues against various injuries and promotes neural regeneration. This review focuses on these new findings and the underlying mechanisms. In particular, we summarize the following key points: (1) the role of delta-opioid receptor in neuroprotection across various models and conditions; (2) the mechanisms of delta-opioid receptor neuroprotection against acute injury; (3) the neuroprotective mechanisms of delta-opioid receptor during prolonged injury; (4) delta-opioid receptor protection against ischemic and degenerative brain diseases and the underlying mechanisms; and (5) the regulation of delta-opioid receptor in neural regeneration. This article aims to provide an overview of delta-opioid receptor-mediated neural protection and regeneration, as well as its potential in treating neurological diseases. 

Key words: Alzheimer’s disease, apoptosis, brain-derived neurotrophic factor, delta-opioid receptor, hypoxiaischemia, ischemic stroke, nerve regeneration, neuroinflammation, neuroprotection, Parkinson’s disease