Home > Publications Database > ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice. > print

001     280906
005     20250907001927.0
024 7 _ |a 10.1038/s41467-025-63211-w
|2 doi
024 7 _ |a pmid:40858618
|2 pmid
024 7 _ |a pmc:PMC12381211
|2 pmc
024 7 _ |a altmetric:180618697
|2 altmetric
037 _ _ |a DZNE-2025-00990
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Lenoel, Isadora
|0 0009-0008-1096-5902
|b 0
245 _ _ |a ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.
260 _ _ |a [London]
|c 2025
|b Springer Nature
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 1756388761_10798
|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 TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations. Conversely, Tbk1 deletion in microglia alters their homeostasis and reactive responses. In both spinal cord and brain, Tbk1 deletion leads to a pro-inflammatory, primed microglial signature with features of ageing and neurodegeneration. While it does not induce or modify ALS-like motor neuron damage, microglial Tbk1 deletion is sufficient to cause early FTD-like social recognition deficits. This phenotype is linked to focal microglial activation and T cell infiltration in the substantia nigra pars reticulata and pallidum. Our results reveal that part of TBK1-linked FTD disease originates from microglial dysfunction.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Protein Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Tbk1 protein, mouse
|0 EC 2.7.1.-
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Protein Serine-Threonine Kinases: genetics
|2 MeSH
650 _ 2 |a Protein Serine-Threonine Kinases: deficiency
|2 MeSH
650 _ 2 |a Protein Serine-Threonine Kinases: metabolism
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: pathology
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: genetics
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: pathology
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: genetics
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: metabolism
|2 MeSH
650 _ 2 |a Frontotemporal Dementia: pathology
|2 MeSH
650 _ 2 |a Motor Neurons: metabolism
|2 MeSH
650 _ 2 |a Motor Neurons: pathology
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Spinal Cord: pathology
|2 MeSH
650 _ 2 |a Spinal Cord: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Autophagy
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Aging
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
700 1 _ |a Ribon, Matthieu
|b 1
700 1 _ |a Lorenc, Félicie
|0 0009-0003-8551-0981
|b 2
700 1 _ |a Diebold, Aurélien
|b 3
700 1 _ |a Philibert, Clementine E
|0 0000-0002-1631-2397
|b 4
700 1 _ |a Robaldo, David
|b 5
700 1 _ |a Badsi, Manel
|b 6
700 1 _ |a Perronnet, Julianne
|b 7
700 1 _ |a Lameth, Julie
|b 8
700 1 _ |a Berriat, Felix
|b 9
700 1 _ |a Misawa, Hidemi
|b 10
700 1 _ |a Coutelier, Marie
|b 11
700 1 _ |a Cassel, Raphaelle
|0 0000-0002-3157-3798
|b 12
700 1 _ |a Sarrazin, Nadège
|b 13
700 1 _ |a Jost-Mousseau, Coline
|b 14
700 1 _ |a Bohl, Delphine
|0 0000-0001-8262-5642
|b 15
700 1 _ |a Millecamps, Stéphanie
|0 0000-0002-0745-6735
|b 16
700 1 _ |a Mallat, Michel
|b 17
700 1 _ |a Brenner, David
|0 P:(DE-2719)9002137
|b 18
700 1 _ |a Weishaupt, Jochen H
|b 19
700 1 _ |a Boillée, Séverine
|0 0000-0001-5518-9005
|b 20
700 1 _ |a Lobsiger, Christian S
|0 0000-0002-4313-010X
|b 21
773 _ _ |a 10.1038/s41467-025-63211-w
|g Vol. 16, no. 1, p. 7951
|0 PERI:(DE-600)2553671-0
|n 1
|p 7951
|t Nature Communications
|v 16
|y 2025
|x 2041-1723
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/280906/files/DZNE-2025-00990.pdf
856 4 _ |u https://pub.dzne.de/record/280906/files/DZNE-2025-00990%20SUP.zip
856 4 _ |u https://pub.dzne.de/record/280906/files/DZNE-2025-00990.pdf?subformat=pdfa
|x pdfa
|y OpenAccess
909 C O |o oai:pub.dzne.de:280906
|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 18
|6 P:(DE-2719)9002137
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
914 1 _ |y 2025
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-01-02
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2025-01-02
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
|0 LIC:(DE-HGF)CCBYNCND4
|2 HGFVOC
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2025-01-02
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-01-02
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-01-02
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Peer review
|d 2024-01-30T07:48:07Z
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1060
|2 StatID
|b Current Contents - Agriculture, Biology and Environmental Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-01-02
920 1 _ |0 I:(DE-2719)5000077
|k Clinical Study Center (Ulm)
|l Clinical Study Center (Ulm)
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)5000077
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21