Work

Pro- and Anti-Inflammatory Neuropeptides and Glia: The Balance Between Neuroprotection and Neuroinflammation

Year: 2025

Type: article

Abstract: Neuropeptides (NPs) are small molecular messengers synthesized in large dense core vesicles (LDCVs) and secreted to the extracellular space. In the central nervous system (CNS), NPs are secreted to the synaptic space, playing crucial roles in modulating neurons, astrocytes, microglia, oligodendrocytes, and other glial cells, through G-protein-coupled receptors, thereby influencing complex multicellular responses. During neuroinflammation, NPs regulate glial and neuronal reactions to inflammatory signals, promoting resolution and preventing chronic, non-resolving inflammation. For example, NPs inhibit apoptosis in neurons and oligodendrocytes while inducing anti-inflammatory effects in microglia and astrocytes, modulating cytokine secretion. Here, we present the notion that neuropeptides could participate in neuroinflammatory progression, altering glial responses, leading to excessive, non-resolutive inflammation when dysregulated. NP signaling—whether excessive or deficient—can disrupt specific cellular processes, leading to pathological inflammation, gliosis, and functional loss—hallmarks of neurodegenerative diseases. Despite their significance, the precise mechanisms underlying NP-mediated effects remain incompletely understood. This review synthesizes experimental and translational evidence highlighting the pivotal role of NPs in resolving neuroinflammation and explores how targeting NPs or their receptors could offer novel therapeutic strategies for neurodegenerative disorders. Further research is needed to elucidate the specific signaling pathways and receptor dynamics involved, which could pave the way for innovative treatments that address the root causes of these debilitating conditions.

Source: Neuroglia

DOI: 10.3390/neuroglia6030035

Authors: Eli J. Futran-Sheinberg, Victoria Urbina, Sofia Nava, Daniel Sanchez, Gilberto Guzmán-Valdivia, Mario A. Zetter

Institution: Universidad La Salle

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,207