Apelin, an endogenous ligand of G protein-coupled receptor APJ, is widely distributed in the central nervous system (CNS). It can be divided into such subtypes as Apelin-13, Apelin-17, and Apelin-36 as they have different amino acid structures. All Apelin is widely studied as an adipokine, showing a significant protective effect through regulating apoptosis, autophagy, oxidative stress, angiogenesis, inflammation, and other pathophysiological processes. As an adipokine, Apelin has been found to play a crucial role in cardiovascular disease development. In this paper, we reviewed the effects and mechanisms of Apelin in treating CNS diseases, such as neurotrauma, stroke, spinal cord injury, primary tumors, neurodegenerative diseases, psychiatric diseases, epilepsy, and pain.

In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injury. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial fission, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis in PC12 cells. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial fission, improve antioxidant capacity, increase ATP production, decrease apoptosis, promote spinal cord morphological repair, maintain the number of nissl bodies, and enhance signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.

The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness—how transplanted cells adapt to new microenvironments and maintain functional stability in vivo—is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

In the early stage of spinal cord injury (SCI), excessive reactive oxygen species (ROS) accumulate at the injury site to establish a microenvironment favoring complex secondary injuries, including cavity formation, and impacting the distal lumbosacral spinal cord. Currently, no definitive clinical treatment is available for SCI. Here, we created an responsive and injectable hydrogel composite (GEL-EXO) by modifying and cross-linking biological macromolecules sodium alginate (SA) and gelatin in the form of embedded exosomes. This GEL-EXO composite integrated the bioactivity of exosomes with the gap-filling function of hydrogels. Our experiments demonstrated that the composite could simultaneously repair spinal cord tissues at the injury site and the distal lumbosacral region, thereby restoring motor function and reinitiating bladder function. This therapeutic strategy may promise a brand-new holistic intervention for SCI.

The mammalian central nervous system (CNS) demonstrates a severely limited capacity for spontaneous neural regeneration after traumatic spinal cord injury (SCI). Structural repair is also highly constrained due to the inhibitory microenvironment. This inherent limitation persists throughout the recovery phase and often leads to severe motor and sensory dysfunction, profoundly impairing patients’ quality of life. Current clinical treatments, including surgical decompression, pharmacological interventions, and rehabilitation therapy, can only partially relieve symptoms. They are not enough to promote neural regeneration and functional recovery. There is an urgent need to develop novel therapeutic approaches to overcome this challenge. This study developed and created an injectable double-network conductive hydrogel, it coordinates iron ions (Fe³⁺) using dynamic Schiff base bonds and metal ion coordination. The conductive hydrogel aids in spinal cord injury repair through various mechanisms, such as reducing glial scar formation, promoting remyelination, and providing neuroprotection. This makes it an injection therapy with promising prospects for clinical translation in the field of nerve regeneration.