Integrated meta-analysis of human astrocytes transcriptomes reveals a candidate recurrent inflammatory signature in response to inflammatory and immune stimuli.

The incidence of nervous system diseases, especially ischemic brain injury and neurodegenerative diseases (such as ischemic stroke, Alzheimer’s disease [AD], Parkinson’s disease [PD], amyotrophic lateral sclerosis) is increasing year by year worldwide, causing a significant health burden on society (GBD 2021 Nervous System Disorders Collaborators, 2024; Li et al., 2024). Ischemic and degenerative brain disorders have become common causes of disability and death among the elderly. Their incidence increases with age, particularly among individuals over 60 years old (Jiang et al., 2025). Although some treatment options are available, many neurological diseases still lack effective therapies, and most existing treatments focus on relieving symptoms (Rashad et al., 2022; Jucker and Walker, 2023; Foltynie et al., 2024). Therefore, the importance of neuroprotection and neural regeneration research has become increasingly prominent. Neuroprotection focuses on delaying or preventing the process of nerve cell death (Hasler and Inta, 2024), while neural regeneration is dedicated to repairing damaged nerve tissue and rebuilding its functional integrity (Saraswathy et al., 2024). These two research directions complement each other and together constitute a key path to breaking through the current treatment bottleneck. In recent years, an increasing number of studies have shown that the delta-opioid receptor (DOR) plays a crucial role in neuroprotection and neural regeneration. Our studies and those of others have consistently shown that activating DOR inhibits neuronal apoptosis, reduces inflammation, and promotes nerve regeneration (Ma et al., 2005; Narita et al., 2006; Hong et al., 2007; Georganta et al., 2013; Tian et al., 2013; Wang et al., 2014; Xu et al., 2025; Qiu et al., 2019; Zhang et al., 2022b), shedding light on new hope for better prevention/treatment of neurological diseases.