From danger to resolution: targeting purinergic signaling in CNS diseases.
9 affiliations
- 1Lille Neuroscience & Cognition (LilNCog), UMR-S1172, Inserm, University of Lille, CHU Lille, Lille, France.
- 2International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Xin-Yi Campus, Taipei, 110, Taiwan.
- 3NeuroTMULille, University of Lille, Lille, France.
- 4Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, New Taipei City, 23561, Taiwan.
- 5International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Shuang-Ho Campus, New Taipei City, 23561, Taiwan.
- 6NeuroTMULille, Taipei Medical University, Taipei, Taiwan.
- 7Lille Neuroscience & Cognition (LilNCog), UMR-S1172, Inserm, University of Lille, CHU Lille, Lille, France. [email protected].
- 8NeuroTMULille, University of Lille, Lille, France. [email protected].
- 9Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, New Taipei City, 23561, Taiwan. [email protected].
Abstract
The central nervous system (CNS) is a dynamic immunological environment, where specialized interfaces, immune reservoirs, and metabolic clearance pathways, such as the glymphatic system, orchestrate immune surveillance and homeostasis. Within this intricate network, purinergic signaling, mediated by nucleotides like ATP and adenosine, emerges as a critical regulator of immune responses, inflammation resolution, and tissue repair. Adenosine, drives immunosuppression and immune exhaustion, shaping the balance between neuroprotection and neurodegeneration. Purinergic signaling influences a diverse array of cells, including platelets, neutrophils, dendritic cells, lymphocytes, macrophages/microglia, astrocytes, oligodendrocytes as well as neurons, each contributing uniquely to CNS immune dynamics. Dysregulation of this signaling network is implicated in major neurodegenerative and neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Recent advances in therapeutic strategies targeting purinergic receptors, such as A2AR and P2X₇, have demonstrated promising clinical potential, offering new avenues for immunomodulation and neuroprotection. This review synthesizes current understanding of purinergic signaling in CNS immunity, explores its role in disease pathogenesis, and discusses innovative therapeutic approaches. By framing purinergic signaling as a tunable "rheostat", we highlight its potential to shift the CNS from danger to resolution, paving the way for precision immunotherapies in neurological disorders.
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BibTeX
@article{degryse2026from,
title = {{From danger to resolution: targeting purinergic signaling in CNS diseases.}},
author = {Camille Degryse and Kirti Gupta and Luc Buée and Thierry Burnouf and David Blum and Ming-Li Chou},
journal = {Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents},
year = {2026},
month = oct,
doi = {10.1007/s00044-026-03583-w},
url = {https://europepmc.org/article/MED/42831935},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - From danger to resolution: targeting purinergic signaling in CNS diseases.
AU - Camille Degryse
AU - Kirti Gupta
AU - Luc Buée
AU - Thierry Burnouf
AU - David Blum
AU - Ming-Li Chou
PY - 2026
DA - 2026/10/05
JO - Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents
DO - 10.1007/s00044-026-03583-w
UR - https://europepmc.org/article/MED/42831935
AB - The central nervous system (CNS) is a dynamic immunological environment, where specialized interfaces, immune reservoirs, and metabolic clearance pathways, such as the glymphatic system, orchestrate immune surveillance and homeostasis. Within this intricate network, purinergic signaling, mediated by nucleotides like ATP and adenosine, emerges as a critical regulator of immune responses, inflammation resolution, and tissue repair. Adenosine, drives immunosuppression and immune exhaustion, shaping the balance between neuroprotection and neurodegeneration. Purinergic signaling influences a diverse array of cells, including platelets, neutrophils, dendritic cells, lymphocytes, macrophages/microglia, astrocytes, oligodendrocytes as well as neurons, each contributing uniquely to CNS immune dynamics. Dysregulation of this signaling network is implicated in major neurodegenerative and neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Recent advances in therapeutic strategies targeting purinergic receptors, such as A2AR and P2X₇, have demonstrated promising clinical potential, offering new avenues for immunomodulation and neuroprotection. This review synthesizes current understanding of purinergic signaling in CNS immunity, explores its role in disease pathogenesis, and discusses innovative therapeutic approaches. By framing purinergic signaling as a tunable "rheostat", we highlight its potential to shift the CNS from danger to resolution, paving the way for precision immunotherapies in neurological disorders.
SN - 1054-2523
SN - 1554-8120
ER -