(−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies
ABSTRACT In tauopathies, defects in autophagy‐lysosomal protein degradation are thought to contribute to the abnormal accumulation of aggregated tau. Recent studies have shown that (−)‐Epicatechin (Epi), a dietary flavonoid belonging to the flavan‐3‐ol subgroup, improves blood flow, modulates metabo...
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2025-04-01
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| Online Access: | https://doi.org/10.1002/mco2.70144 |
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| author | Yanqing Wu Ting Li Xingjun Jiang Jianmin Ling Zaihua Zhao Jiahui Zhu Chongyang Chen Qian Liu Xifei Yang Xuefeng Shen Rong Ma Gang Li Gongping Liu |
| author_facet | Yanqing Wu Ting Li Xingjun Jiang Jianmin Ling Zaihua Zhao Jiahui Zhu Chongyang Chen Qian Liu Xifei Yang Xuefeng Shen Rong Ma Gang Li Gongping Liu |
| author_sort | Yanqing Wu |
| collection | DOAJ |
| description | ABSTRACT In tauopathies, defects in autophagy‐lysosomal protein degradation are thought to contribute to the abnormal accumulation of aggregated tau. Recent studies have shown that (−)‐Epicatechin (Epi), a dietary flavonoid belonging to the flavan‐3‐ol subgroup, improves blood flow, modulates metabolic profiles, and prevents oxidative damage. However, less research has explored the effects of Epi on tauopathies. Here, we found that Epi rescued cognitive deficits in P301S tau transgenic mice, a model exhibiting characteristics of tauopathies like frontotemporal dementia and Alzheimer's disease, and attenuated tau pathology through autophagy activation. Proteomic and biochemical analyses revealed that P301S mice exhibit deficits in autophagosome formation via modulating mTOR, consequently inhibiting autophagy. Epi inhibited the mTOR signaling pathway to promote autophagosome formation, which is essential for the clearance of tau aggregation. By using chloroquine (CQ) to inhibit autophagy in vivo, we further confirmed that Epi induced tau degradation via the autophagy pathway. Lastly, Epi administration was also found to improve cognition by reversing spine decrease and neuron loss, as well as attenuating neuroinflammation. Our findings suggest that Epi promoted tau clearance by activating autophagy, indicating its potential as a promising therapeutic candidate for tauopathies. |
| format | Article |
| id | doaj-art-5f8d5bb42ac04047b45595e83b0de835 |
| institution | OA Journals |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-5f8d5bb42ac04047b45595e83b0de8352025-08-20T02:17:34ZengWileyMedComm2688-26632025-04-0164n/an/a10.1002/mco2.70144(−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of TauopathiesYanqing Wu0Ting Li1Xingjun Jiang2Jianmin Ling3Zaihua Zhao4Jiahui Zhu5Chongyang Chen6Qian Liu7Xifei Yang8Xuefeng Shen9Rong Ma10Gang Li11Gongping Liu12Department of Neurology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathophysiology School of Basic Medicine Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaDepartment of Emergency Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment School of Public Health Air Force Medical University Xi'an ChinaDepartment of Neurology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Nuclear Medicine Ministry of Health Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine Wuxi ChinaDepartment of Pathophysiology School of Basic Medicine Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaKey Laboratory of Modern Toxicology of Shenzhen Shenzhen Center for Disease Control and Prevention Shenzhen ChinaDepartment of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment School of Public Health Air Force Medical University Xi'an ChinaDepartment of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Pathophysiology School of Basic Medicine Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaABSTRACT In tauopathies, defects in autophagy‐lysosomal protein degradation are thought to contribute to the abnormal accumulation of aggregated tau. Recent studies have shown that (−)‐Epicatechin (Epi), a dietary flavonoid belonging to the flavan‐3‐ol subgroup, improves blood flow, modulates metabolic profiles, and prevents oxidative damage. However, less research has explored the effects of Epi on tauopathies. Here, we found that Epi rescued cognitive deficits in P301S tau transgenic mice, a model exhibiting characteristics of tauopathies like frontotemporal dementia and Alzheimer's disease, and attenuated tau pathology through autophagy activation. Proteomic and biochemical analyses revealed that P301S mice exhibit deficits in autophagosome formation via modulating mTOR, consequently inhibiting autophagy. Epi inhibited the mTOR signaling pathway to promote autophagosome formation, which is essential for the clearance of tau aggregation. By using chloroquine (CQ) to inhibit autophagy in vivo, we further confirmed that Epi induced tau degradation via the autophagy pathway. Lastly, Epi administration was also found to improve cognition by reversing spine decrease and neuron loss, as well as attenuating neuroinflammation. Our findings suggest that Epi promoted tau clearance by activating autophagy, indicating its potential as a promising therapeutic candidate for tauopathies.https://doi.org/10.1002/mco2.70144autophagy(−)‐EpicatechinFTDPmemory deficitstauopathies |
| spellingShingle | Yanqing Wu Ting Li Xingjun Jiang Jianmin Ling Zaihua Zhao Jiahui Zhu Chongyang Chen Qian Liu Xifei Yang Xuefeng Shen Rong Ma Gang Li Gongping Liu (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies MedComm autophagy (−)‐Epicatechin FTDP memory deficits tauopathies |
| title | (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies |
| title_full | (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies |
| title_fullStr | (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies |
| title_full_unstemmed | (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies |
| title_short | (−)‐Epicatechin Rescues Memory Deficits by Activation of Autophagy in a Mouse Model of Tauopathies |
| title_sort | epicatechin rescues memory deficits by activation of autophagy in a mouse model of tauopathies |
| topic | autophagy (−)‐Epicatechin FTDP memory deficits tauopathies |
| url | https://doi.org/10.1002/mco2.70144 |
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