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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.
- Source :
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Journal of integrative neuroscience [J Integr Neurosci] 2024 Sep 23; Vol. 23 (9), pp. 175. - Publication Year :
- 2024
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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.)
- Subjects :
- Animals
Male
Mice
Dopaminergic Neurons drug effects
Dopaminergic Neurons metabolism
Glycogen Synthase Kinase 3 beta metabolism
Glycogen Synthase Kinase 3 beta drug effects
Mice, Inbred C57BL
Parkinsonian Disorders metabolism
Parkinsonian Disorders drug therapy
Synucleinopathies metabolism
Synucleinopathies drug therapy
alpha-Synuclein metabolism
alpha-Synuclein drug effects
Benzaldehydes pharmacology
Benzaldehydes administration & dosage
Disease Models, Animal
Neuroprotective Agents pharmacology
Neuroprotective Agents administration & dosage
Wnt Signaling Pathway drug effects
Wnt Signaling Pathway physiology
Subjects
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