ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model
Summary: Amyloid-β (Aβ) plays an important role in the neuropathology of Alzheimer’s disease (AD), but some factors promoting Aβ generation and Aβ oligomer (Aβo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723006356 |
| _version_ | 1797807023102885888 |
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| author | Ya-ru Huang Xi-xiu Xie Jing Yang Xiao-ying Sun Xiao-yun Niu Cheng-gang Yang Ling-jie Li Lun Zhang Dan Wang Chun-yu Liu Sheng-jie Hou Chen-yang Jiang Yu-ming Xu Rui-tian Liu |
| author_facet | Ya-ru Huang Xi-xiu Xie Jing Yang Xiao-ying Sun Xiao-yun Niu Cheng-gang Yang Ling-jie Li Lun Zhang Dan Wang Chun-yu Liu Sheng-jie Hou Chen-yang Jiang Yu-ming Xu Rui-tian Liu |
| author_sort | Ya-ru Huang |
| collection | DOAJ |
| description | Summary: Amyloid-β (Aβ) plays an important role in the neuropathology of Alzheimer’s disease (AD), but some factors promoting Aβ generation and Aβ oligomer (Aβo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aβ generation by decreasing the expression of APP, PS1, and β-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aβo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aβ production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aβos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment. |
| first_indexed | 2024-03-13T06:16:16Z |
| format | Article |
| id | doaj.art-0fc98a5893394101a62f5db921a73f36 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T06:16:16Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0fc98a5893394101a62f5db921a73f362023-06-11T04:14:28ZengElsevierCell Reports2211-12472023-06-01426112624ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse modelYa-ru Huang0Xi-xiu Xie1Jing Yang2Xiao-ying Sun3Xiao-yun Niu4Cheng-gang Yang5Ling-jie Li6Lun Zhang7Dan Wang8Chun-yu Liu9Sheng-jie Hou10Chen-yang Jiang11Yu-ming Xu12Rui-tian Liu13State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaDepartment of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Henan Medical Key Laboratory of Neurogenetic and Neurodegenerative Disease, Zhengzhou 450052, Henan, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Ningxia University, Yinchuan 750021, Ningxia, ChinaDepartment of BigData, Beijing Medintell Bioinformatic Technology Co., Ltd., Beijing 100081, China; Department of Research and Development, Gu’an Bojian Bio-Technology Co., Ltd., Langfang 065000, Hebei, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaDepartment of BigData, Beijing Medintell Bioinformatic Technology Co., Ltd., Beijing 100081, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Shandong Agricultural University, Tai’an 271000, Shandong, ChinaState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, ChinaDepartment of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Key Laboratory of Cerebrovascular Disease of Henan Province, Zhengzhou 450052, Henan, China; Corresponding authorState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Corresponding authorSummary: Amyloid-β (Aβ) plays an important role in the neuropathology of Alzheimer’s disease (AD), but some factors promoting Aβ generation and Aβ oligomer (Aβo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aβ generation by decreasing the expression of APP, PS1, and β-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aβo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aβ production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aβos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.http://www.sciencedirect.com/science/article/pii/S2211124723006356CP: Neuroscience |
| spellingShingle | Ya-ru Huang Xi-xiu Xie Jing Yang Xiao-ying Sun Xiao-yun Niu Cheng-gang Yang Ling-jie Li Lun Zhang Dan Wang Chun-yu Liu Sheng-jie Hou Chen-yang Jiang Yu-ming Xu Rui-tian Liu ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model Cell Reports CP: Neuroscience |
| title | ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model |
| title_full | ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model |
| title_fullStr | ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model |
| title_full_unstemmed | ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model |
| title_short | ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer’s disease-like mouse model |
| title_sort | arhgap11a mediates amyloid β generation and neuropathology in an alzheimer s disease like mouse model |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723006356 |
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