STAT3 ameliorates truncated tau-induced cognitive deficits
Proteolytic cleavage of tau by asparagine endopeptidase (AEP) creates tau-N368 fragments, which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer's disease patients. Nonetheless, the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear. Evidence suggests that signal transduction and activator of transcription-3 (STAT3) is associated with modulating synaptic plasticity, cell apoptosis, and cognitive function. Using luciferase reporter assays, electrophoretic mobility shift assays, western blotting, and immunofluorescence, we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus. Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss, thereby improving the cognitive deficits in tau-N368 mice. Moreover, in tau-N368 mice, activation of STAT3 increased N-methyl-D-aspartic acid receptor levels, decreased Bcl-2 levels, reversed synaptic damage and neuronal loss, and thereby alleviated cognitive deficits caused by tau-N368. Taken together, STAT3 plays a critical role in truncated tau-related neuropathological changes. This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits. STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Neural regeneration research - 19(2023), 4 vom: 16. Apr., Seite 915-922 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Bingge [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer’s disease |
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| Anmerkungen: |
Date Revised 24.11.2023 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.4103/1673-5374.382253 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363360379 |
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| 520 | |a Proteolytic cleavage of tau by asparagine endopeptidase (AEP) creates tau-N368 fragments, which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer's disease patients. Nonetheless, the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear. Evidence suggests that signal transduction and activator of transcription-3 (STAT3) is associated with modulating synaptic plasticity, cell apoptosis, and cognitive function. Using luciferase reporter assays, electrophoretic mobility shift assays, western blotting, and immunofluorescence, we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus. Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss, thereby improving the cognitive deficits in tau-N368 mice. Moreover, in tau-N368 mice, activation of STAT3 increased N-methyl-D-aspartic acid receptor levels, decreased Bcl-2 levels, reversed synaptic damage and neuronal loss, and thereby alleviated cognitive deficits caused by tau-N368. Taken together, STAT3 plays a critical role in truncated tau-related neuropathological changes. This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits. STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a N-methyl-D-aspartic acid receptor | |
| 650 | 4 | |a STAT3 | |
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| 650 | 4 | |a neurodegenerative disease | |
| 650 | 4 | |a neuron loss | |
| 650 | 4 | |a synapse | |
| 650 | 4 | |a tau-N368 | |
| 700 | 1 | |a Wan, Huali |e verfasserin |4 aut | |
| 700 | 1 | |a Maierwufu, Maimaitijian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a He, Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Gongping |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Xiaoyue |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Qiong |e verfasserin |4 aut | |
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