1. Vanillin Mitigates the MPTP-Induced α-Synucleinopathy in a Mouse Model of Parkinson's Disease: Insights into the Involvement of Wnt/β-Catenin Signaling.
- Author
-
Rani L and Mondal AC
- 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
- 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
129 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., Methods: In our previous study utilizing 1-methyl-4-phenylpyridinium (MPP+ )-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+ /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-Ser129 -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., 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., 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., (© 2024 The Author(s). Published by IMR Press.)- Published
- 2024
- Full Text
- View/download PDF