Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain
The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer’s disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the pr...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/878123 |
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| author | Zhong-Sen Qu Liang Li Xiao-Jiang Sun Yu-Wu Zhao Jin Zhang Zhi Geng Jian-Liang Fu Qing-Guo Ren |
| author_facet | Zhong-Sen Qu Liang Li Xiao-Jiang Sun Yu-Wu Zhao Jin Zhang Zhi Geng Jian-Liang Fu Qing-Guo Ren |
| author_sort | Zhong-Sen Qu |
| collection | DOAJ |
| description | The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer’s disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-β peptides (Aβ) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And Aβ40 and Aβ42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of Aβ overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of Aβ and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects. |
| format | Article |
| id | doaj-art-848cbeb2458e46b99f8d794e1084b21c |
| institution | Kabale University |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-848cbeb2458e46b99f8d794e1084b21c2025-02-03T06:12:29ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/878123878123Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat BrainZhong-Sen Qu0Liang Li1Xiao-Jiang Sun2Yu-Wu Zhao3Jin Zhang4Zhi Geng5Jian-Liang Fu6Qing-Guo Ren7Department of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Neurology, The Central Hospital Affiliated Qingdao University, Qingdao 266042, ChinaDepartment of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Neurology, The Sixth People’s Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, ChinaDepartment of Pathophysiology, Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaThe pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer’s disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-β peptides (Aβ) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And Aβ40 and Aβ42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of Aβ overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of Aβ and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.http://dx.doi.org/10.1155/2014/878123 |
| spellingShingle | Zhong-Sen Qu Liang Li Xiao-Jiang Sun Yu-Wu Zhao Jin Zhang Zhi Geng Jian-Liang Fu Qing-Guo Ren Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain The Scientific World Journal |
| title | Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain |
| title_full | Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain |
| title_fullStr | Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain |
| title_full_unstemmed | Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain |
| title_short | Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain |
| title_sort | glycogen synthase kinase 3 regulates production of amyloid β peptides and tau phosphorylation in diabetic rat brain |
| url | http://dx.doi.org/10.1155/2014/878123 |
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