Searching across hundreds of databases
Aging is a major risk factor for both genetic and sporadic neurodegenerative disorders. However, it is unclear how aging interacts with genetic predispositions to promote neurodegeneration. Here, we investigate how partial loss of function of TBK1, a major genetic cause for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comorbidity, leads to age-dependent neurodegeneration. We show that TBK1 is an endogenous inhibitor of RIPK1 and the embryonic lethality of Tbk1-/- mice is dependent on RIPK1 kinase activity. In aging human brains, another endogenous RIPK1 inhibitor, TAK1, exhibits a marked decrease in expression. We show that in Tbk1+/- mice, the reduced myeloid TAK1 expression promotes all the key hallmarks of ALS/FTD, including neuroinflammation, TDP-43 aggregation, axonal degeneration, neuronal loss, and behavior deficits, which are blocked upon inhibition of RIPK1. Thus, aging facilitates RIPK1 activation by reducing TAK1 expression, which cooperates with genetic risk factors to promote the onset of ALS/FTD.
Pubmed ID: 30146158 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets MAP3K7
View all literature mentionsThis polyclonal targets RIP3 antibody
View all literature mentionsThis monoclonal targets Phospho-IKKα/β (Ser176/180)
View all literature mentionsThis polyclonal targets IKKalpha
View all literature mentionsThis monoclonal targets GST (B-14)
View all literature mentionsThis polyclonal targets DYKDDDK
View all literature mentionsThis polyclonal targets NFKBIA
View all literature mentionsThis polyclonal targets p38 MAPK
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis monoclonal targets IKKbeta (D30C6) Rabbit mAb
View all literature mentionsThis monoclonal targets TAK1 (D94D7) Rabbit mAb
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets CX3CR1
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets Phospho-TAK1 (Thr184/187)
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets β-Actin polyclonal antibody
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets Phospho-I B (Ser32)
View all literature mentionsThis polyclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets Choline Acetyltransferase
View all literature mentionsThis monoclonal targets NeuN clone A60 Alexa Fluor 488 conjugated
View all literature mentionsThis polyclonal targets TDP-43
View all literature mentionsThis monoclonal targets FADD antibody [EPR5030]
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsThis monoclonal targets RIP
View all literature mentionsThis monoclonal targets RIP
View all literature mentionsThis monoclonal targets Phospho-TBK1/NAK (Ser172)
View all literature mentionsThis polyclonal targets Tbk1
View all literature mentionsCell line Jurkat E6.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospho-IKKα/β (Ser176/180)
View all literature mentionsThis monoclonal targets MAP3K7
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
