SUN11602, a bFGF mimetic, modulated neuroinflammation, apoptosis and calcium-binding proteins in an in vivo model of MPTP-induced nigrostriatal degeneration.
Animals
Apoptosis
Benzamides
Calcium-Binding Proteins
/ metabolism
Disease Models, Animal
Dopaminergic Neurons
Fibroblast Growth Factor 2
MPTP Poisoning
/ drug therapy
Mice
Mice, Inbred C57BL
Neurodegenerative Diseases
/ drug therapy
Neuroinflammatory Diseases
Neuroprotective Agents
/ pharmacology
Parkinson Disease
/ metabolism
Phenylenediamines
Ca2+ homeostasis
Calbindin
MPTP-mouse model
Neuroprotective
Parkinson’s disease (PD)
SUN11602
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
07 May 2022
07 May 2022
Historique:
received:
21
12
2021
accepted:
01
04
2022
entrez:
7
5
2022
pubmed:
8
5
2022
medline:
11
5
2022
Statut:
epublish
Résumé
Parkinson's disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration. Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction. The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.
Sections du résumé
BACKGROUND
BACKGROUND
Parkinson's disease (PD) is the second most frequent neurodegenerative disease. PD etiopathogenesis is multifactorial and not yet fully known, however, the scientific world advised the establishment of neuroinflammation among the possible risk factors. In this field, basic fibroblast growth factor/fibroblast growth factor receptor-1 (bFGF/FGFR1) could be a promising way to treat CNS-mediated inflammation; unfortunately, the use of bFGF as therapeutic agent is limited by its side effects. The novel synthetic compound SUN11602 exhibited neuroprotective activities like bFGF. With this perspective, this study aimed to evaluate the effect of SUN11602 administration in a murine model of MPTP-induced dopaminergic degeneration.
METHODS
METHODS
Specifically, nigrostriatal degeneration was induced by intraperitoneal injection of MPTP (80 mg/kg). SUN11602 (1 mg/kg, 2.5 mg/kg, and 5 mg/kg) was administered daily by oral gavage starting from 24 h after the first administration of MPTP. Mice were killed 7 days after MPTP induction.
RESULTS
RESULTS
The results obtained showed that SUN11602 administration significantly reduced the alteration of PD hallmarks, attenuating the neuroinflammatory state via modulation of glial activation, NF-κB pathway, and cytokine overexpression. Furthermore, we demonstrated that SUN11602 treatment rebalanced Ca
CONCLUSION
CONCLUSIONS
Therefore, in the light of these findings, SUN11602 could be considered a valuable pharmacological strategy for PD.
Identifiants
pubmed: 35526035
doi: 10.1186/s12974-022-02457-3
pii: 10.1186/s12974-022-02457-3
pmc: PMC9080217
doi:
Substances chimiques
4-((4-(((4-amino-2,3,5,6-tetramethylanilino)acetyl)(methyl)amino)-1-piperidinyl)methyl)benzamide
0
Benzamides
0
Calcium-Binding Proteins
0
Neuroprotective Agents
0
Phenylenediamines
0
Fibroblast Growth Factor 2
103107-01-3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Informations de copyright
© 2022. The Author(s).
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