bp(GO:"cellular senescence")
Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037
Transcriptomic analyses of NFT-containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
The cell cycle protein p21, encoded by Cdkn1a, is upregulated in many senescent cell types and has been associated with DNA damage during neuronal aging (Jurk et al., 2012) PubMed:30126037
Relative to the existing neuronal population at this advanced age, gene expression of the NFT-associated senescence gene array was reduced by DQ (P = 0.0006; Figure S6a) PubMed:30126037
The astrocyte protein GFAP was unchanged, while microglia Iba1 expression was elevated (Iba1: 40%, P = 0.0013; Figure S6b-d) suggesting that DQ-mediated neuroprotection and decreased SASP was not derived from a reduction in pro-inflammatory glia (astrocytes or microglia) but instead associated with fewer NFT-containing neurons PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
TauNFT mouse brains displayed significantly elevated histone γ-H2ax, a sensitive marker of both double-stranded DNA breaks and cellular senescence (Sedelnikova et al., 2004) (P = 0.0056; Figure 1d-e) PubMed:30126037
The reduced tau pathology corresponded with 60% lower Cdkn2a expression (P = 0.0041, Figure 4a), decreased SASP (Figure S4) and decreased brain atrophy (tauNFT-Mapt0/0: 0.4058 ± 0.009 versus age-matched tauNFT Maptwt/wt: 0.3451 ± 0.0116; 17.5% difference, P = 0.0143, Figure 4b) PubMed:30126037
TauNFT mice develop aggressive tauopathy with NFT formation in early life, and show a senescence-associated transcriptomic profile with NFT onset (Figure 1c) PubMed:30126037
Experimental data from various studies indicate that tau pathology may be associated with cellular senescence, a fundamental aging mechanism shown to contribute to several chronic diseases (recent review Kirkland and Tchkonia, 2017) PubMed:30126037
Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Aß load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels of total tau in the cortex, hippocampus and cerebellum. PubMed:29221819
Mitochondrial dysfunction is obligatory for SASP production and cellular senescence (Correia-Melo et al., 2016; Hutter et al., 2004) PubMed:30126037
Transcriptomic analyses of NFT-containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction PubMed:30126037
Transcriptomic analyses of NFT-containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction PubMed:30126037
This complex stress response induces a near permanent cell cycle arrest, adaptations to maintain survival, cellular remodeling, metabolic dysfunction and disruption to surrounding tissue to the secretion of toxic molecules (Childs et al., 2016) PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
Transcriptomic analyses of NFT-containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction PubMed:30126037
This complex stress response induces a near permanent cell cycle arrest, adaptations to maintain survival, cellular remodeling, metabolic dysfunction and disruption to surrounding tissue to the secretion of toxic molecules (Childs et al., 2016) PubMed:30126037
Transcriptomic analyses of NFT-containing neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction PubMed:30126037
This complex stress response induces a near permanent cell cycle arrest, adaptations to maintain survival, cellular remodeling, metabolic dysfunction and disruption to surrounding tissue to the secretion of toxic molecules (Childs et al., 2016) PubMed:30126037
Cdkn2a transcript level, a hallmark measure of senescence, directly correlated with brain atrophy and NFT burden in mice PubMed:30126037
Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037
Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037
Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037
Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037
Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037
Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037
Experimental data from various studies indicate that tau pathology may be associated with cellular senescence, a fundamental aging mechanism shown to contribute to several chronic diseases (recent review Kirkland and Tchkonia, 2017) PubMed:30126037
This complex stress response induces a near permanent cell cycle arrest, adaptations to maintain survival, cellular remodeling, metabolic dysfunction and disruption to surrounding tissue to the secretion of toxic molecules (Childs et al., 2016) PubMed:30126037
This complex stress response induces a near permanent cell cycle arrest, adaptations to maintain survival, cellular remodeling, metabolic dysfunction and disruption to surrounding tissue to the secretion of toxic molecules (Childs et al., 2016) PubMed:30126037
Senescence-inducing stressors often inflict DNA-damage that drives production of the SASP (Rodier et al., 2009) PubMed:30126037
The cell cycle protein p21, encoded by Cdkn1a, is upregulated in many senescent cell types and has been associated with DNA damage during neuronal aging (Jurk et al., 2012) PubMed:30126037
The cell cycle protein p21, encoded by Cdkn1a, is upregulated in many senescent cell types and has been associated with DNA damage during neuronal aging (Jurk et al., 2012) PubMed:30126037
Similarly, elevated expression of the cyclin dependent kinase inhibitor 2a, Cdkn2a, is one of the most robust markers of cellular senescence, and its protein product, p16INK4A, co-localizes with NFTs in human AD (Arendt et al., 1996) PubMed:30126037
NFkB regulates the pro-survival, pro-inflammatory SASP gene expression profile characteristic of cellular senescence (Salminen & Kaarniranta, 2011) PubMed:30126037
Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Aß load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels of total tau in the cortex, hippocampus and cerebellum. PubMed:29221819
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.