CCR1 Antagonism by BX471 Attenuates Neuroinflammation and Apoptosis: Preliminary Findings From an In Vitro Model of Neuronal Injury
6 affiliations
- 1School of Advanced Studies, Center of Neuroscience University of Camerino Camerino Italy
- 2Department of Chemical, Biological, Pharmaceutical and Environmental Sciences Viale Ferdinando Stagno d'Alcontres 31, 98166, University of Messina Messina Italy
- 3Research Operative Unit of Neuropharmacology and Translational Neurosciences Oasi Research Institute, IRCCS Troina Italy
- 4Genetics and Pharmacogenetics Unit “Gaetano Martino” University Hospital Messina Italy
- 5Departmental Faculty of Medicine UniCamillus‐Saint Camillus International University of Health Sciences Rome Italy
- 6IRCCS San Camillo Hospital Venice Italy
Abstract
Neuronal injury as traumatic brain injury (TBI) triggers a complex pathophysiological cascade involving inflammatory and apoptosis processes. BX471 is a selective C‐C chemokine receptor type 1 (CCR1) antagonist that showed a promising effect in modulating neuroinflammation in central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effect of BX471 on the inflammatory pathway and apoptotic process in an in vitro model of induced‐neuronal injury using SH‐SY5Y neuroblastoma cells. Firstly, cytotoxicity was assessed by MTT assay to determine the optimal effective concentrations and the best temporal window for BX471 activity. Then, SH‐SY5Y cells were subjected to a scratch injury to mimic a neuronal injury and were treated with different concentrations of BX471. ELISA and qRT‐PCR were used to analyze the expression level of the CCR1/chemokines axis (CCR1, RANTES, MIP‐1α), inflammatory markers (TNF‐α, IL‐1β, IL‐6, NF‐κB, IκBα, and PPAR𝛾), and the apoptotic pathway (Bcl2, BAX, P53, and cleaved caspase 3). The results showed that BX471 significantly improved the cell viability and inhibited the CCR1/chemokine axis and pro‐inflammatory cytokines as well as modulating the apoptotic course. Overall, these results suggest that BX471 may reduce neuronal injury by inhibiting neuroinflammation and apoptosis, and that its neuroprotective effect, mediated through the CCR1 signaling pathway, deserves further investigation in in vivo models.
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BibTeX
@article{hasan2026ccr1,
title = {{CCR1 Antagonism by BX471 Attenuates Neuroinflammation and Apoptosis: Preliminary Findings From an In Vitro Model of Neuronal Injury}},
author = {Ahmed Hasan and Deborah Mannino and Sarah Adriana Scuderi and Lucia Buccarello and Emanuela Esposito and Giuseppe Caruso and Alessio Ardizzone},
journal = {Pharmacology Research \& Perspectives},
year = {2026},
month = oct,
doi = {10.1002/prp2.70332},
url = {https://doi.org/10.1002/prp2.70332},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - CCR1 Antagonism by BX471 Attenuates Neuroinflammation and Apoptosis: Preliminary Findings From an In Vitro Model of Neuronal Injury
AU - Ahmed Hasan
AU - Deborah Mannino
AU - Sarah Adriana Scuderi
AU - Lucia Buccarello
AU - Emanuela Esposito
AU - Giuseppe Caruso
AU - Alessio Ardizzone
PY - 2026
DA - 2026/10/26
JO - Pharmacology Research & Perspectives
DO - 10.1002/prp2.70332
UR - https://doi.org/10.1002/prp2.70332
AB - Neuronal injury as traumatic brain injury (TBI) triggers a complex pathophysiological cascade involving inflammatory and apoptosis processes. BX471 is a selective C‐C chemokine receptor type 1 (CCR1) antagonist that showed a promising effect in modulating neuroinflammation in central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effect of BX471 on the inflammatory pathway and apoptotic process in an in vitro model of induced‐neuronal injury using SH‐SY5Y neuroblastoma cells. Firstly, cytotoxicity was assessed by MTT assay to determine the optimal effective concentrations and the best temporal window for BX471 activity. Then, SH‐SY5Y cells were subjected to a scratch injury to mimic a neuronal injury and were treated with different concentrations of BX471. ELISA and qRT‐PCR were used to analyze the expression level of the CCR1/chemokines axis (CCR1, RANTES, MIP‐1α), inflammatory markers (TNF‐α, IL‐1β, IL‐6, NF‐κB, IκBα, and PPAR𝛾), and the apoptotic pathway (Bcl2, BAX, P53, and cleaved caspase 3). The results showed that BX471 significantly improved the cell viability and inhibited the CCR1/chemokine axis and pro‐inflammatory cytokines as well as modulating the apoptotic course. Overall, these results suggest that BX471 may reduce neuronal injury by inhibiting neuroinflammation and apoptosis, and that its neuroprotective effect, mediated through the CCR1 signaling pathway, deserves further investigation in in vivo models.
SN - 2052-1707
ER -