کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4932589 | 1433525 | 2017 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra](/preview/png/4932589.png)
چکیده انگلیسی
Sigma-1 receptor (Ï1R) is expressed in dopaminergic neurons of substantia nigra. Here, we show that Ï1R knockout (Ï1Râ/â) mice, at age 6-12 months, appeared with age-related loss of dopaminergic neurons and decline of motor coordination. Levels of α-synuclein (αSyn) oligomers and fibrillar αSyn in substantia nigra of Ï1Râ/â mice were age-dependently increased without the changes in αSyn monomers. The phosphorylation of αSyn monomers or oligomers in dopaminergic neurons was enhanced in Ï1Râ/â mice. Levels of phosphorylated eIF2a and C/EBP homologous protein expression were elevated in Ï1Râ/â mice with decline of proteasome activity. Inhibition of endoplasmic reticulum stress by salubrinal recovered the αSyn phosphorylation and proteasome activity and prevented early oligomerization of αSyn in Ï1Râ/â mice. Rifampicin reduced the late increase of αSyn oligomers in Ï1Râ/â mice. Rifampicin or salubrinal could reduce the loss of dopaminergic neurons in Ï1Râ/â mice and improved their motor coordination. The results indicate that the Ï1R deficiency through enhanced aggregation and phosphorylation of αSyn causes the loss of dopaminergic neurons leading to the decline of motor coordination.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 59, November 2017, Pages 171-183
Journal: Neurobiology of Aging - Volume 59, November 2017, Pages 171-183
نویسندگان
Juan Hong, Ling Wang, Tingting Zhang, Baofeng Zhang, Ling Chen,