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Vanillin Mitigates the MPTP-Induced α-Synucleinopathy in a Mouse Model of Parkinson's Disease: Insights into the Involvement of Wnt/β-Catenin Signaling.

Authors :
Rani L
Mondal AC
Source :
Journal of integrative neuroscience [J Integr Neurosci] 2024 Sep 23; Vol. 23 (9), pp. 175.
Publication Year :
2024

Abstract

Background: The abnormal aggregation of α-synuclein (α-syn) in the substantia nigra pars compacta (SNpc) region of the brain is characteristic of Parkinson's disease (PD), leading to the selective demise of neurons. Modifications in the post-translational processing of α-syn, phosphorylation at Ser <superscript>129</superscript> in particular, are implicated in α-syn aggregation and are considered key hallmarks of PD. Furthermore, dysregulated Wnt/β-catenin signaling, influenced by glycogen synthase kinase-3 beta (GSK-3β), is implicated in PD pathogenesis. Inhibition of GSK-3β holds promise in promoting neuroprotection by enhancing the Wnt/β-catenin pathway.<br />Methods: In our previous study utilizing 1-methyl-4-phenylpyridinium (MPP <superscript>+</superscript> )-administered differentiated SH-SY5Y cells and a PD mouse model, we explored Vanillin's neuroprotective properties and related mechanisms against neuronal loss induced by MPP <superscript>+</superscript> /1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. In the current study, we elucidated the mitigating effects of Vanillin on motor impairments, P-Ser <superscript>129</superscript> -α-syn expression, Wnt/β-catenin signaling, and autophagic neuron death induced by MPTP in a mouse model of PD by performing motor function tests, western blot analysis and immunostaining.<br />Results: Our results show that Vanillin effectively modulated the motor dysfunctions, GSK-3β expression, and activity, activated the Wnt/β-catenin signaling, and reduced autophagic neuronal demise in the MPTP-lesioned mice, highlighting its neuroprotective effects.<br />Conclusions: These findings underscore the complex interplay between α-syn pathology, GSK-3β, Wnt/β-catenin signaling, and autophagic-cell death in PD pathogenesis. Targeting these pathways, particularly with Vanillin, can be a promising therapeutic strategy for restoring dopaminergic (DA-ergic) neuronal homeostasis and slowing the progression of PD. Further research is crucial to resolving existing disputes and translating these discoveries into effective therapeutic interventions for PD patients.<br /> (© 2024 The Author(s). Published by IMR Press.)

Details

Language :
English
ISSN :
0219-6352
Volume :
23
Issue :
9
Database :
MEDLINE
Journal :
Journal of integrative neuroscience
Publication Type :
Academic Journal
Accession number :
39344237
Full Text :
https://doi.org/10.31083/j.jin2309175