Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum
Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutan...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnins.2018.00301/full |
| _version_ | 1811261950761369600 |
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| author | Yanan Luan Xiangpeng Ren Xiangpeng Ren Wu Zheng Wu Zheng Zhenhai Zeng Yingzi Guo Zhidong Hou Wei Guo Wei Guo Xingjun Chen Fei Li Jiang-Fan Chen Jiang-Fan Chen Jiang-Fan Chen |
| author_facet | Yanan Luan Xiangpeng Ren Xiangpeng Ren Wu Zheng Wu Zheng Zhenhai Zeng Yingzi Guo Zhidong Hou Wei Guo Wei Guo Xingjun Chen Fei Li Jiang-Fan Chen Jiang-Fan Chen Jiang-Fan Chen |
| author_sort | Yanan Luan |
| collection | DOAJ |
| description | Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine—a strongly protective environment factor as suggested by epidemiological evidence—may represent a novel pharmacological therapy for PD by targeting autophagy pathway. |
| first_indexed | 2024-04-12T19:16:05Z |
| format | Article |
| id | doaj.art-aad3c8e3cf444c76ab4eb3df0a83f94d |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-12T19:16:05Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-aad3c8e3cf444c76ab4eb3df0a83f94d2022-12-22T03:19:45ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-05-011210.3389/fnins.2018.00301336493Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse StriatumYanan Luan0Xiangpeng Ren1Xiangpeng Ren2Wu Zheng3Wu Zheng4Zhenhai Zeng5Yingzi Guo6Zhidong Hou7Wei Guo8Wei Guo9Xingjun Chen10Fei Li11Jiang-Fan Chen12Jiang-Fan Chen13Jiang-Fan Chen14Molecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Optometry and Vision Science, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Optometry and Vision Science, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Optometry and Vision Science, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMolecular Neuropharmacology Laboratory, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Optometry and Vision Science, Wenzhou, ChinaDepartment of Neurology, Boston University School of Medicine, Boston, MA, United StatesDespite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine—a strongly protective environment factor as suggested by epidemiological evidence—may represent a novel pharmacological therapy for PD by targeting autophagy pathway.http://journal.frontiersin.org/article/10.3389/fnins.2018.00301/fullα-synucleincaffeineautophagymacroautophagyα-synucleinopathyParkinson's disease |
| spellingShingle | Yanan Luan Xiangpeng Ren Xiangpeng Ren Wu Zheng Wu Zheng Zhenhai Zeng Yingzi Guo Zhidong Hou Wei Guo Wei Guo Xingjun Chen Fei Li Jiang-Fan Chen Jiang-Fan Chen Jiang-Fan Chen Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum Frontiers in Neuroscience α-synuclein caffeine autophagy macroautophagy α-synucleinopathy Parkinson's disease |
| title | Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum |
| title_full | Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum |
| title_fullStr | Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum |
| title_full_unstemmed | Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum |
| title_short | Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum |
| title_sort | chronic caffeine treatment protects against α synucleinopathy by reestablishing autophagy activity in the mouse striatum |
| topic | α-synuclein caffeine autophagy macroautophagy α-synucleinopathy Parkinson's disease |
| url | http://journal.frontiersin.org/article/10.3389/fnins.2018.00301/full |
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