Neuropharmacology 2015-06-01

Neuroprotective effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone in MPTP induced Parkinsonism model in mice.

Zhili Ren, Nan Yang, Chao Ji, Ji Zheng, Tao Wang, Yanyong Liu, Pingping Zuo

Index: Neuropharmacology 93 , 209-18, (2015)

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Abstract

Parkinson's disease (PD) is a neurological disorder characterized by degeneration of nigrostriatal dopaminergic (DAergic) system. Present treatment targeting to DAergic system solely ameliorated the symptoms but failed to retard the DAergic neuron degeneration, therefore new therapeutic methods aiming at preventing or delaying the neurodegenerative process are urgently needed. In the present study, we found that 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone (RD-1), a compound derived from rhodanine, protected DAergicneurons from neurotoxicity of MPTP/MPP(+). Firstly, RD-1 significantly improved the locomotor ability in the MPTP mice model, and elevated the tyrosine hydroxylase (TH) positive cell numbers in substantianigra pars compacta (SNpc) and the integrated optical density (IOD) of TH-positive nerve fibers in striatum respectively. Since mitochondrial dysfunction plays an important role in pathogenesis of PD, thereby we investigated the molecular mechanisms of RD-1 against MPTP/MPP(+) neurotoxicity, focusing on its effects on the mitochondrial dysfunction. Immunoblotting analysis showed that RD-1 significantly elevated the Parkin and Miro2 expression levels in acute MPTP treated mice, and improved mitochondrial membrane potential and ATP synthesis in MPP(+)-treated Neuro-2a cells. Moreover, RD-1attenuated impaired mitochondrial transport and vesicle release dysfunction evoked by MPP(+) cytotoxicity in cultured primary mesencephalic neurons. Taken together, these results indicate that improving the mitochondrial dysfunction may be a good choice to delay the neurodegenerative progression commonly associated with PD. Copyright © 2015 Elsevier Ltd. All rights reserved.