Role of Aβ in Alzheimer’s-related synaptic dysfunction
Synaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate rec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.964075/full |
| _version_ | 1828356868843503616 |
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| author | Huiqin Zhang Xuefan Jiang Lina Ma Wei Wei Zehui Li Surui Chang Jiayu Wen Jiahui Sun Hao Li Hao Li |
| author_facet | Huiqin Zhang Xuefan Jiang Lina Ma Wei Wei Zehui Li Surui Chang Jiayu Wen Jiahui Sun Hao Li Hao Li |
| author_sort | Huiqin Zhang |
| collection | DOAJ |
| description | Synaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate receptors, such as NMDA and AMPA receptors, which mediates calcium dyshomeostasis and damages synapse plasticity characterized by long-term potentiation (LTP) suppression and long-term depression (LTD) enhancement. As Aβ stimulates and Ca2+ influx, microglial cells and astrocyte can be activated and release cytokines, which reduces glutamate uptake and further impair synapse function. Besides, extracellular glutamate accumulation induced by Aβ mediates synapse toxicity resulting from reduced glutamate receptors and glutamate spillovers. Aβ also mediates synaptic dysfunction by acting on various signaling pathways and molecular targets, disrupting mitochondria and energy metabolism. In addition, Aβ overdeposition aggravates the toxic damage of hyperphosphorylated tau to synapses. Synaptic dysfunction plays a critical role in cognitive impairment of AD. The review addresses the possible mechanisms by which Aβ mediates AD-related synaptic impairment from distant perspectives. |
| first_indexed | 2024-04-14T03:06:23Z |
| format | Article |
| id | doaj.art-8de01b5fd20a4f1e8dc6778206ff7c88 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-14T03:06:23Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8de01b5fd20a4f1e8dc6778206ff7c882022-12-22T02:15:43ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.964075964075Role of Aβ in Alzheimer’s-related synaptic dysfunctionHuiqin Zhang0Xuefan Jiang1Lina Ma2Wei Wei3Zehui Li4Surui Chang5Jiayu Wen6Jiahui Sun7Hao Li8Hao Li9Institute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBeijing University of Chinese Medicine, Beijing, ChinaInstitute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaBeijing University of Chinese Medicine, Beijing, ChinaWangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaInstitute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaWangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaSynaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate receptors, such as NMDA and AMPA receptors, which mediates calcium dyshomeostasis and damages synapse plasticity characterized by long-term potentiation (LTP) suppression and long-term depression (LTD) enhancement. As Aβ stimulates and Ca2+ influx, microglial cells and astrocyte can be activated and release cytokines, which reduces glutamate uptake and further impair synapse function. Besides, extracellular glutamate accumulation induced by Aβ mediates synapse toxicity resulting from reduced glutamate receptors and glutamate spillovers. Aβ also mediates synaptic dysfunction by acting on various signaling pathways and molecular targets, disrupting mitochondria and energy metabolism. In addition, Aβ overdeposition aggravates the toxic damage of hyperphosphorylated tau to synapses. Synaptic dysfunction plays a critical role in cognitive impairment of AD. The review addresses the possible mechanisms by which Aβ mediates AD-related synaptic impairment from distant perspectives.https://www.frontiersin.org/articles/10.3389/fcell.2022.964075/fullsynaptic dysfunctionAlzheimer’s diseaseβ-amyloidglutamate receptorssynaptic plasticitysynapse toxicity |
| spellingShingle | Huiqin Zhang Xuefan Jiang Lina Ma Wei Wei Zehui Li Surui Chang Jiayu Wen Jiahui Sun Hao Li Hao Li Role of Aβ in Alzheimer’s-related synaptic dysfunction Frontiers in Cell and Developmental Biology synaptic dysfunction Alzheimer’s disease β-amyloid glutamate receptors synaptic plasticity synapse toxicity |
| title | Role of Aβ in Alzheimer’s-related synaptic dysfunction |
| title_full | Role of Aβ in Alzheimer’s-related synaptic dysfunction |
| title_fullStr | Role of Aβ in Alzheimer’s-related synaptic dysfunction |
| title_full_unstemmed | Role of Aβ in Alzheimer’s-related synaptic dysfunction |
| title_short | Role of Aβ in Alzheimer’s-related synaptic dysfunction |
| title_sort | role of aβ in alzheimer s related synaptic dysfunction |
| topic | synaptic dysfunction Alzheimer’s disease β-amyloid glutamate receptors synaptic plasticity synapse toxicity |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.964075/full |
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