Central neuropeptides as key modulators of astrocyte function in neurodegenerative and neuropsychiatric disorders

Central neuropeptides are small proteins or peptides primarily produced and released by neurons. They act as neurotransmitters, neuromodulators, and neuroregulators within the central nervous system (CNS). Numerous studies have demonstrated that these neuropeptides play a role in both normal neurophysiological processes and pathological conditions. Astrocytes, the most abundant glial cells in the CNS, are crucial for maintaining brain function and health, and they contribute significantly to the development of CNS disorders-especially neurodegenerative and neuropsychiatric diseases. Previous research suggests that central neuropeptides influence astrocyte activity by regulating their proliferation, morphology, and secretory functions, among other aspects, thereby impacting the pathogenesis of these disorders. Based on preclinical evidence, both central neuropeptides and their receptors are emerging as promising targets for treating CNS disorders. In this review, we examine the effects of select central neuropeptides-including neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), cholecystokinin (CCK), corticotropin-releasing hormone (CRH), angiotensin (Ang), oxytocin (OXT), orexin (OX)/hypocretin (HCRT), and glucagon-like peptide-1 (GLP-1)-on astrocyte state transitions. Our aim is to provide novel insights that could inform the clinical treatment of neurodegenerative and neuropsychiatric disorders.