Home > Publications Database > RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease > print

001     154788
005     20230915092314.0
024 7 _ |a pmid:34131105
|2 pmid
024 7 _ |a 10.1038/s41419-021-03899-y
|2 doi
024 7 _ |a altmetric:107663390
|2 altmetric
024 7 _ |a 34131105
|2 pmid
024 7 _ |a pmc:PMC8206344
|2 pmc
037 _ _ |a DZNE-2021-00368
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Pérez-Sisqués, Leticia
|0 0000-0002-9682-9811
|b 0
245 _ _ |a RTP801/REDD1 contributes to neuroinflammation severity and memory impairments in Alzheimer’s disease
260 _ _ |a London [u.a.]
|c 2021
|b Nature Publishing Group
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1623923427_14474
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a RTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death. Its downregulation in Parkinson's and Huntington's disease models ameliorates the pathological phenotypes. In the context of Alzheimer's disease (AD), the coding gene for RTP801, DDIT4, is responsive to Aβ and modulates its cytotoxicity in vitro. Also, RTP801 mRNA levels are increased in AD patients' lymphocytes. However, the involvement of RTP801 in the pathophysiology of AD has not been yet tested. Here, we demonstrate that RTP801 levels are increased in postmortem hippocampal samples from AD patients. Interestingly, RTP801 protein levels correlated with both Braak and Thal stages of the disease and with GFAP expression. RTP801 levels are also upregulated in hippocampal synaptosomal fractions obtained from murine 5xFAD and rTg4510 mice models of the disease. A local RTP801 knockdown in the 5xFAD hippocampal neurons with shRNA-containing AAV particles ameliorates cognitive deficits in 7-month-old animals. Upon RTP801 silencing in the 5xFAD mice, no major changes were detected in hippocampal synaptic markers or spine density. Importantly, we found an unanticipated recovery of several gliosis hallmarks and inflammasome key proteins upon neuronal RTP801 downregulation in the 5xFAD mice. Altogether our results suggest that RTP801 could be a potential future target for theranostic studies since it could be a biomarker of neuroinflammation and neurotoxicity severity of the disease and, at the same time, a promising therapeutic target in the treatment of AD.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|x 0
|f POF IV
588 _ _ |a Dataset connected to CrossRef, Journals: pub.dzne.de
650 _ 2 |a Alzheimer Disease: complications
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Case-Control Studies
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Encephalitis: etiology
|2 MeSH
650 _ 2 |a Encephalitis: genetics
|2 MeSH
650 _ 2 |a Encephalitis: pathology
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Memory Disorders: etiology
|2 MeSH
650 _ 2 |a Memory Disorders: genetics
|2 MeSH
650 _ 2 |a Memory Disorders: pathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Neuroimmunomodulation: genetics
|2 MeSH
650 _ 2 |a Neurotoxicity Syndromes: etiology
|2 MeSH
650 _ 2 |a Neurotoxicity Syndromes: genetics
|2 MeSH
650 _ 2 |a Neurotoxicity Syndromes: pathology
|2 MeSH
650 _ 2 |a Severity of Illness Index
|2 MeSH
650 _ 2 |a Transcription Factors: physiology
|2 MeSH
700 1 _ |a Sancho-Balsells, Anna
|b 1
700 1 _ |a Solana-Balaguer, Júlia
|b 2
700 1 _ |a Campoy-Campos, Genís
|b 3
700 1 _ |a Vives-Isern, Marcel
|b 4
700 1 _ |a Soler-Palazón, Ferran
|b 5
700 1 _ |a Anglada-Huguet, Marta
|0 P:(DE-2719)9000008
|b 6
|u dzne
700 1 _ |a López-Toledano, Miguel-Ángel
|b 7
700 1 _ |a Mandelkow, Eva-Maria
|0 P:(DE-2719)2541658
|b 8
|u dzne
700 1 _ |a Alberch, Jordi
|0 0000-0002-8684-2721
|b 9
700 1 _ |a Giralt, Albert
|0 0000-0001-5334-0963
|b 10
700 1 _ |a Malagelada, Cristina
|0 0000-0001-7185-436X
|b 11
773 _ _ |a 10.1038/s41419-021-03899-y
|g Vol. 12, no. 6, p. 616
|0 PERI:(DE-600)2541626-1
|n 6
|p 616
|t Cell death & disease
|v 12
|y 2021
|x 2041-4889
856 4 _ |u https://www.nature.com/articles/s41419-021-03899-y
856 4 _ |u https://pub.dzne.de/record/154788/files/7815.pdf
|y OpenAccess
856 4 _ |u https://pub.dzne.de/record/154788/files/7815.pdf?subformat=pdfa
|x pdfa
|y OpenAccess
909 C O |o oai:pub.dzne.de:154788
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 P:(DE-2719)9000008
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 8
|6 P:(DE-2719)2541658
913 0 _ |a DE-HGF
|b Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-342
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms and Model Systems
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2021
915 _ _ |a Creative Commons Attribution CC BY (No Version)
|0 LIC:(DE-HGF)CCBYNV
|2 V:(DE-HGF)
|b DOAJ
|d 2021-02-03
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2021-02-03
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2021-02-03
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2021-02-03
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2021-02-03
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2021-02-03
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b CELL DEATH DIS : 2021
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2021-02-14T16:18:53Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2021-02-14T16:18:53Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Blind peer review
|d 2021-02-14T16:18:53Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2022-11-17
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2022-11-17
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b CELL DEATH DIS : 2021
|d 2022-11-17
920 1 _ |0 I:(DE-2719)1013015
|k AG Mandelkow 2
|l Cell and Animal Models of Neurodegeneration
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1013015
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21