Early and sustained altered expression of aging-related genes in young 3xTg-AD mice.

Abstract:

:Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Gatta V,D'Aurora M,Granzotto A,Stuppia L,Sensi SL

doi

10.1038/cddis.2014.11

subject

Has Abstract

pub_date

2014-02-13 00:00:00

pages

e1054

issn

2041-4889

pii

cddis201411

journal_volume

5

pub_type

杂志文章
  • Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis.

    abstract::The role of autophagy in cancer onset and progression appears still controversial. On one hand, autophagy allows cancer cell to survive in unfavorable environmental conditions, on the other hand, once internal energy resources are exhausted, it leads to cell death. In addition, autophagy interpheres with cell cycle pr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0864-7

    authors: Buccarelli M,Marconi M,Pacioni S,De Pascalis I,D'Alessandris QG,Martini M,Ascione B,Malorni W,Larocca LM,Pallini R,Ricci-Vitiani L,Matarrese P

    更新日期:2018-08-06 00:00:00

  • CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer.

    abstract::Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1894-5

    authors: Liu Y,Zhang X,Lin J,Chen Y,Qiao Y,Guo S,Yang Y,Zhu G,Pan Q,Wang J,Sun F

    更新日期:2019-09-09 00:00:00

  • MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression.

    abstract::Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.485

    authors: Jeong BC,Kang IH,Hwang YC,Kim SH,Koh JT

    更新日期:2014-11-20 00:00:00

  • Structural insight into an evolutionarily ancient programmed cell death regulator - the crystal structure of marine sponge BHP2 bound to LB-Bak-2.

    abstract::Sponges of the porifera family harbor some of the evolutionary most ancient orthologs of the B-cell lymphoma-2 (Bcl-2) family, a protein family critical to regulation of apoptosis. The genome of the sponge Geodia cydonium contains the putative pro-survival Bcl-2 homolog BHP2, which protects sponge tissue as well as ma...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.469

    authors: Caria S,Hinds MG,Kvansakul M

    更新日期:2017-01-12 00:00:00

  • DEPTOR is a direct p53 target that suppresses cell growth and chemosensitivity.

    abstract::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03185-3

    authors: Cui D,Dai X,Gong L,Chen X,Wang L,Xiong X,Zhao Y

    更新日期:2020-11-12 00:00:00

  • Loss of MADD expression inhibits cellular growth and metastasis in anaplastic thyroid cancer.

    abstract::Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, e...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1351-5

    authors: Saini S,Sripada L,Tulla K,Kumar P,Yue F,Kunda N,Maker AV,Prabhakar BS

    更新日期:2019-02-13 00:00:00

  • Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death.

    abstract::The mitogen-activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1079-7

    authors: Syc-Mazurek SB,Rausch RL,Fernandes KA,Wilson MP,Libby RT

    更新日期:2018-10-26 00:00:00

  • H. pylori infection confers resistance to apoptosis via Brd4-dependent BIRC3 eRNA synthesis.

    abstract::H. pylori infection is one of the leading causes of gastric cancer and the pathogenicity of H. pylori infection is associated with its ability to induce chronic inflammation and apoptosis resistance. While H. pylori infection-induced expression of pro-inflammatory cytokines for chronic inflammation is well studied, th...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02894-z

    authors: Chen Y,Sheppard D,Dong X,Hu X,Chen M,Chen R,Chakrabarti J,Zavros Y,Peek RM,Chen LF

    更新日期:2020-08-21 00:00:00

  • PKCθ-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization.

    abstract::Pathological retinal neovascularization is the most common cause of vision loss. PKCθ has been shown to play a role in type 2 diabetes, which is linked to retinal neovascularization. Based on these clues, we have studied the role of PKCθ and its downstream target genes JunB and VEGFR3 in retinal neovascularization usi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2522-0

    authors: Kumar R,Mani AM,Singh NK,Rao GN

    更新日期:2020-05-07 00:00:00

  • Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.

    abstract::Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. The...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.103

    authors: De Simone V,Bevivino G,Sedda S,Izzo R,Laudisi F,Dinallo V,Franzè E,Colantoni A,Ortenzi A,Salvatori S,Rossi P,Sica GS,Fantini MC,Stolfi C,Monteleone G

    更新日期:2017-03-16 00:00:00

  • GluR6-FasL-Trx2 mediates denitrosylation and activation of procaspase-3 in cerebral ischemia/reperfusion in rats.

    abstract::Global cerebral ischemia/reperfusion (I/R) facilitates the activation of procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have remained uncharacterized. Protein S-nitrosylation and denitrosylation is an important reversible posttranslational modification, which is a common mechanism in signal tra...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.299

    authors: Sun N,Hao JR,Li XY,Yin XH,Zong YY,Zhang GY,Gao C

    更新日期:2013-08-15 00:00:00

  • Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5.

    abstract::The voltage-gated K+ channel has key roles in the vasculature and in atrial excitability and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1....

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.568

    authors: Al-Owais MM,Hettiarachchi NT,Boyle JP,Scragg JL,Elies J,Dallas ML,Lippiat JD,Steele DS,Peers C

    更新日期:2017-11-02 00:00:00

  • Gefitinib targets ZAP-70-expressing chronic lymphocytic leukemia cells and inhibits B-cell receptor signaling.

    abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.391

    authors: Dielschneider RF,Xiao W,Yoon JY,Noh E,Banerji V,Li H,Marshall AJ,Johnston JB,Gibson SB

    更新日期:2014-10-02 00:00:00

  • HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level.

    abstract::Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02946-4

    authors: Zhang J,Qiu WQ,Zhu H,Liu H,Sun JH,Chen Y,Shen H,Qian CL,Shen ZY

    更新日期:2020-09-19 00:00:00

  • Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells.

    abstract::The aim of our study was to investigate the role of autophagy, a homeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins, in regulating the survival of mesangial cells treated with advanced glycation end products (AGEs). In the present study, AGEs induced mitochondrial depolar...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.322

    authors: Xu L,Fan Q,Wang X,Zhao X,Wang L

    更新日期:2016-11-03 00:00:00

  • GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

    abstract::Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.104

    authors: L'Episcopo F,Drouin-Ouellet J,Tirolo C,Pulvirenti A,Giugno R,Testa N,Caniglia S,Serapide MF,Cisbani G,Barker RA,Cicchetti F,Marchetti B

    更新日期:2016-04-28 00:00:00

  • Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization.

    abstract::The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0284-8

    authors: Li M,Lai X,Zhao Y,Zhang Y,Li M,Li D,Kong J,Zhang Y,Jing P,Li H,Qin H,Shen L,Yao L,Li J,Dou K,Zhang J

    更新日期:2018-02-14 00:00:00

  • Survival control of oligodendrocyte progenitor cells requires the transcription factor 4 during olfactory bulb development.

    abstract::A proper number of oligodendrocytes in the nerve system is essential for neuronal functions. In the olfactory bulb (OB), enriched oligodendrocytes are crucial for olfactory information processing. However, how the precise number of oligodendrocytes in the OB is regulated remains elusive. Here we identified that the tr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03371-3

    authors: Zhang Y,Cai Y,Wang Y,Deng X,Zhao Y,Zhang Y,Xie Y

    更新日期:2021-01-18 00:00:00

  • The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer.

    abstract::Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-021-03414-3

    authors: Eyermann CE,Haley JD,Alexandrova EM

    更新日期:2021-01-26 00:00:00

  • Preclinical studies using cisplatin/carboplatin to restore the Enzalutamide sensitivity via degrading the androgen receptor splicing variant 7 (ARv7) to further suppress Enzalutamide resistant prostate cancer.

    abstract::The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients' survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) sp...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02970-4

    authors: Chou FJ,Lin C,Tian H,Lin W,You B,Lu J,Sahasrabudhe D,Huang CP,Yang V,Yeh S,Niu Y,Chang C

    更新日期:2020-11-02 00:00:00

  • The thiosemicarbazone Me2NNMe2 induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition.

    abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1102-z

    authors: Hager S,Korbula K,Bielec B,Grusch M,Pirker C,Schosserer M,Liendl L,Lang M,Grillari J,Nowikovsky K,Pape VFS,Mohr T,Szakács G,Keppler BK,Berger W,Kowol CR,Heffeter P

    更新日期:2018-10-15 00:00:00

  • Amlexanox, a selective inhibitor of IKBKE, generates anti-tumoral effects by disrupting the Hippo pathway in human glioblastoma cell lines.

    abstract::Glioblastoma multiforme (GBM) is the most prevalent form of malignant brain tumor. Amlexanox, a novel compound, has been shown to have anti-cancer potential. In this study, the anti-tumoral effects and the underlying mechanisms of amlexanox were investigated. Amlexanox significantly suppressed proliferation and invasi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.396

    authors: Liu Y,Lu J,Zhang Z,Zhu L,Dong S,Guo G,Li R,Nan Y,Yu K,Zhong Y,Huang Q

    更新日期:2017-08-31 00:00:00

  • The long non-coding RNA SNHG1 promotes glioma progression by competitively binding to miR-194 to regulate PHLDA1 expression.

    abstract::Long non-coding RNAs (lncRNAs) play a vital role in tumourigenesis, including that of glioma. Small nucleolar RNA host gene 1 (SNHG1) is a relatively novel lncRNA that is involved in the development of multiple human tumours. However, its underlying molecular mechanism in glioma has not been completely clarified. In t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1698-7

    authors: Liu L,Shi Y,Shi J,Wang H,Sheng Y,Jiang Q,Chen H,Li X,Dong J

    更新日期:2019-06-12 00:00:00

  • Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that inhibits the Wnt/β-catenin pathway.

    abstract::The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) d...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0128-y

    authors: Li M,Han Y,Zhou H,Li X,Lin C,Zhang E,Chi X,Hu J,Xu H

    更新日期:2018-01-24 00:00:00

  • A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis.

    abstract::Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspa...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.219

    authors: Kim JH,Lee DK,Kim J,Choi S,Park W,Ha KS,Kim TH,Choe J,Won MH,Kwon YG,Kim YM

    更新日期:2017-05-18 00:00:00

  • DDX3 DEAD-box RNA helicase plays a central role in mitochondrial protein quality control in Leishmania.

    abstract::DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.315

    authors: Padmanabhan PK,Zghidi-Abouzid O,Samant M,Dumas C,Aguiar BG,Estaquier J,Papadopoulou B

    更新日期:2016-10-13 00:00:00

  • Annonacin promotes selective cancer cell death via NKA-dependent and SERCA-dependent pathways.

    abstract::In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and see...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0772-x

    authors: Yiallouris A,Patrikios I,Johnson EO,Sereti E,Dimas K,De Ford C,Fedosova NU,Graier WF,Sokratous K,Kyriakou K,Stephanou A

    更新日期:2018-07-09 00:00:00

  • LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5.

    abstract::Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung aden...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1811-y

    authors: Jia Y,Duan Y,Liu T,Wang X,Lv W,Wang M,Wang J,Liu L

    更新日期:2019-07-30 00:00:00

  • Crosstalk between Dpp and Tor signaling coordinates autophagy-dependent midgut degradation.

    abstract::The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicl...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1368-9

    authors: Denton D,Xu T,Dayan S,Nicolson S,Kumar S

    更新日期:2019-02-08 00:00:00

  • Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1.

    abstract::The wogonin-containing herb Scutellaria baicalensis has successfully been used for curing various diseases in traditional Chinese medicine. Wogonin has been shown to induce apoptosis in different cancer cells and to suppress growth of human cancer xenografts in vivo. However, its direct targets remain unknown. In this...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.66

    authors: Polier G,Ding J,Konkimalla BV,Eick D,Ribeiro N,Köhler R,Giaisi M,Efferth T,Desaubry L,Krammer PH,Li-Weber M

    更新日期:2011-07-21 00:00:00