Cyclosporine A and MnTMPyP Alleviate α-Synuclein Expression and Aggregation in Cypermethrin-Induced Parkinsonism

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• 作者：Sonal Agrawal ; Anubhuti Dixit ; Ashish Singh ; Pratibha Tripathi…
• 关键词：α ; Synuclein ; Mitochondrial dysfunction ; Oxidative damage ; cypermethrin ; induced Parkinsonism ; Cyclosporine A ; MnTMPyP
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：52
• 期：3
• 页码：1619-1628
• 全文大小：3,628 KB
• 参考文献：1.Mishra AK, Ur Rasheed MS, Shukla S, Tripathi MK, Dixit A, Singh MP (2014) Aberrant autophagy and Parkinsonism: does correction rescue from disease progression? Mol Neurobiol. doi:10.-007/?s12035-014-8744-3
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  8.Agrawal S, Singh A, Tripathi P, Mishra M, Singh PK, Singh MP (2014) Cypermethrin-induced nigrostriatal dopaminergic neurodegeneration alters the mitochondrial function: a proteomics study. Mol Neurobiol. doi:10.-007/?s12035-014-8696-7
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  15.Dixit A, Srivastava G, Verma D, Mishra M, Singh PK, Prakash O, Singh MP (2013) Minocycline, levodopa and MnTMPyP induced changes in the mitochondrial proteome profile of MPTP and maneb and paraquat mice models of Parkinson’s disease. Biochim Biophys Acta 1832:1227-240CrossRef PubMed
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• 作者单位：Sonal Agrawal (1) (2)
  Anubhuti Dixit (1)
  Ashish Singh (1)
  Pratibha Tripathi (1)
  Dhirendra Singh (1)
  Devendra Kumar Patel (1)
  Mahendra Pratap Singh (1) (2)
  
  1. CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box No. 80, Lucknow, 226001, Uttar Pradesh, India
  2. Academy of Scientific and Innovative Research, New Delhi, 110025, India
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Cypermethrin induces the mitochondrial dysfunction and oxidative damage to the nigrostriatal dopaminergic neurons leading to Parkinsonism in rats. Despite α-synuclein aggregation is reported to be critical in Parkinson’s disease, its role and alliance with the mitochondrial dysfunction and oxidative damage leading to cypermethrin-induced Parkinsonism have not yet been deciphered. The present study aimed to examine the effect of cypermethrin on the expression and aggregation of α-synuclein and its subsequent connection with oxidative damage and mitochondrial dysfunction leading to the nigrostriatal dopaminergic neurodegeneration in the presence or absence of a mitochondrial membrane transition pore opening inhibitor, cyclosporine A and a superoxide dismutase/catalase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). The expression of α-synuclein, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE)-modified proteins, mitochondrial dysfunction-dependent apoptotic proteins, nitrite content, lipid peroxidation (LPO) and number of tyrosine hydroxylase (TH)-positive neurons were estimated in the substantia nigra and dopamine content in the striatum of control and treated rats employing standard procedures. Cypermethrin augmented the expression of α-synuclein, 3-NT, 4-HNE-modified proteins, caspase-3, mitochondrial Bax and cytosolic cytochrome-c along with nitrite and LPO and reduced the expression of cytosolic Bax, mitochondrial cytochrome-c, dopamine and number of TH-positive neurons. Cyclosporine A or MnTMPyP alleviated the expression and aggregation of α-synuclein along with indicators of the mitochondrial dysfunction, oxidative damage and dopaminergic neurodegeneration. The results demonstrate that cypermethrin induces α-synuclein expression and aggregation while cyclosporine A or MnTMPyP rescues from α-synuclein over-expression and aggregation along with the mitochondrial dysfunction and oxidative damage leading to Parkinsonism in rats. Keywords α-Synuclein Mitochondrial dysfunction Oxidative damage, cypermethrin-induced Parkinsonism Cyclosporine A MnTMPyP