title: Neuroprotective effects of 5-(4-hydroxy-3-dimethoxybenzylidene)-thiazolidinone in MPTP induced Parkinsonism model in mice.
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.
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors: Zhili
authors: Z
authors: Ren
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors: Nan
authors: N
authors: Yang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors: Chao
authors: C
authors: Ji
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors: Ji
authors: J
authors: Zheng
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
authors: Tao
authors: T
authors: Wang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address: liuyanyong@126.com.
authors: Yanyong
authors: Y
authors: Liu
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences &School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China. Electronic address: pingping_zuo@126.com.
authors: Pingping
authors: P
authors: Zuo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001597:Benzylidene Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009498:Neurotoxins / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C569195:5-(4-hydroxy-3,5-dimethylbenzylidene)thiazolidine-2,4-dione; D001597:Benzylidene Compounds; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D045162:Thiazolidinediones; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; C493504:Rhot2 protein, mouse; D020741:rho GTP-Binding Proteins
keywords: 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone; MPP(+); MPTP; Mitochondrial dysfunction; Parkinson's disease