Abstract
Parkinson’s disease (PD) is one of the most prevalent and life-threatening neurodegenerative disease and mainly characterized by lack of sufficient dopaminergic neurons in the substantia nigra pars compacta (SNc). Although current treatments help to alleviate clinical symptoms, effective therapies preventing neuronal loss remain scarce. Tovophyllin A (TA), one of the xanthones extracted from Garcinia mangostana L. (GM), has recently been reported to play a beneficial role in the therapy of neurodegenerative diseases. In our research, we explored whether TA has protective effects on dopaminergic neurons in PD models. We found that TA significantly reduced apoptotic cell death in primary cortical neurons treated with 1-methyl-4-phenyl pyridinium (MPP+) or paraquat (PQ) in the in vitro PD model. In an in vivo acute PD model induced by 1-methyl4-phenyl-1,2,3,5-tetrahydropyridine (MPTP) treatment, TA also attenuated the resulting behavioral dysfunctions and dopaminergic neuron loss. In the collected brain tissues, TA increased the phosphorylation of Akt and GSK-3β, which may be related to TA-mediated dopaminergic neuronal protective effects. In summary, our results illustrated that TA is a powerful cytoprotective agent for dopaminergic neurons in the MPTP-induced PD model, suggesting TA as a possible therapeutic candidate for PD.
Highlights
Parkinson’s disease (PD), a long-term and complex movement disorder, is hallmarked by the classical motor features, including slowness of movement, resting tremors, stiffness, and postural instability (Dauer and Przedborski, 2003; Dexter and Jenner, 2013; Kalia and Lang, 2015)
The results indicated that Tovophyllin A (TA) modulated the pathway of Akt/GSK-3β, which may contribute to TA-induced dopaminergic neuron protection
The protective effects of TA on MPP+-toxicity and PQtoxicity in primary cultured neurons were investigated by MTT assay
Summary
Parkinson’s disease (PD), a long-term and complex movement disorder, is hallmarked by the classical motor features, including slowness of movement, resting tremors, stiffness, and postural instability (Dauer and Przedborski, 2003; Dexter and Jenner, 2013; Kalia and Lang, 2015). The precise pathogenic mechanism of the neurodegeneration in PD is not yet fully understood, various factors that alone or together, such as oxidative stress (OS), neuroinflammation and mitochondrial toxins, Neuroprotection of Tovophyllin A in Parkinson’s Disease have been implicated to the progressive impairments of dopaminergic neurons (Moon and Paek, 2015; Morris and Berk, 2015; Hu et al, 2019). MPP+, the active metabolite of MPTP, is transported into dopaminergic neurons by the dopamine transporter (DAT) It is isolated into synaptosomal vesicles or enriched in the mitochondria, where it promotes the production of free radicals (Jackson-Lewis and Przedborski, 2007; Motyl et al, 2018). When response to the toxicology of MPP+ and MPTP, necrotic and apoptotic mechanisms of cell death occurred
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