REDD1 Is Involved in Amyloid beta-Induced Synaptic Dysfunction and Memory Impairment
DC Field | Value | Language |
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dc.contributor.author | Yi, J.H. | - |
dc.contributor.author | Kwon, H. | - |
dc.contributor.author | Cho, E. | - |
dc.contributor.author | Jeon, J. | - |
dc.contributor.author | Lee, J. | - |
dc.contributor.author | Lee, Y.C. | - |
dc.contributor.author | Cho, J.H. | - |
dc.contributor.author | Jun, M. | - |
dc.contributor.author | Moon, M. | - |
dc.contributor.author | Ryu, J.H. | - |
dc.contributor.author | Kim, J.-S. | - |
dc.contributor.author | Choi, J.W. | - |
dc.contributor.author | Park, S.J. | - |
dc.contributor.author | Lee, S. | - |
dc.contributor.author | Kim, D.H. | - |
dc.date.available | 2021-01-18T00:40:11Z | - |
dc.date.created | 2020-12-28 | - |
dc.date.issued | 2020-12 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79750 | - |
dc.description.abstract | Alzheimer’s disease (AD) is a neurodegenerative disease characterized by neurological dysfunction, including memory impairment, attributed to the accumulation of amyloid β (Aβ) in the brain. Although several studies reported possible mechanisms involved in Aβ pathology, much remains unknown. Previous findings suggested that a protein regulated in development and DNA damage response 1 (REDD1), a stress-coping regulator, is an Aβ-responsive gene involved in Aβ cytotoxicity. However, we still do not know how Aβ increases the level of REDD1 and whether REDD1 mediates Aβ-induced synaptic dysfunction. To elucidate this, we examined the effect of Aβ on REDD1-expression using acute hippocampal slices from mice, and the effect of REDD1 short hairpin RNA (shRNA) on Aβ-induced synaptic dysfunction. Lastly, we observed the effect of REDD1 shRNA on memory deficit in an AD-like mouse model. Through the experiments, we found that Aβ-incubated acute hippocampal slices showed increased REDD1 levels. Moreover, Aβ injection into the lateral ventricle increased REDD1 levels in the hippocampus. Anisomycin, but not actinomycin D, blocked Aβ-induced increase in REDD1 levels in the acute hippocampal slices, suggesting that Aβ may increase REDD1 translation rather than transcription. Aβ activated Fyn/ERK/S6 cascade, and inhibitors for Fyn/ERK/S6 or mGluR5 blocked Aβ-induced REDD1 upregulation. REDD1 inducer, a transcriptional activator, and Aβ blocked synaptic plasticity in the acute hippocampal slices. REDD1 inducer inhibited mTOR/Akt signaling. REDD1 shRNA blocked Aβ-induced synaptic deficits. REDD1 shRNA also blocked Aβ-induced memory deficits in passive-avoidance and object-recognition tests. Collectively, these results demonstrate that REDD1 participates in Aβ pathology and could be a target for AD therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | International Journal of Molecular Sciences | - |
dc.title | REDD1 Is Involved in Amyloid beta-Induced Synaptic Dysfunction and Memory Impairment | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000602877600001 | - |
dc.identifier.doi | 10.3390/ijms21249482 | - |
dc.identifier.bibliographicCitation | International Journal of Molecular Sciences, v.21, no.24, pp.1 - 13 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85097794973 | - |
dc.citation.endPage | 13 | - |
dc.citation.startPage | 1 | - |
dc.citation.title | International Journal of Molecular Sciences | - |
dc.citation.volume | 21 | - |
dc.citation.number | 24 | - |
dc.contributor.affiliatedAuthor | Choi, J.W. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Alzheimer’s disease | - |
dc.subject.keywordAuthor | Aβ | - |
dc.subject.keywordAuthor | Hippocampal long-term potentiation | - |
dc.subject.keywordAuthor | Learning and memory | - |
dc.subject.keywordAuthor | REDD1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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