Central and Peripheral Mechanisms in ApoE4-Driven Diabetic Pathology.


:Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer's disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we employed a model of APOE-targeted replacement mice and high-fat diet (HFD)-induced insulin resistance to investigate diabetic mechanisms associated with apoE4 pathology and the extent to which they are driven by peripheral and central processes. Results obtained revealed an intriguing pattern, in which under basal conditions, apoE4 mice display impaired glucose and insulin tolerance and decreased insulin secretion, as well as cognitive and sensorimotor characteristics relative to apoE3 mice, while the HFD impairs apoE3 mice without significantly affecting apoE4 mice. Measurements of weight and fasting blood glucose levels increased in a time-dependent manner following the HFD, though no effect of genotype was observed. Interestingly, sciatic electrophysiological and skin intra-epidermal nerve fiber density (IENFD) peripheral measurements were not affected by the APOE genotype or HFD, suggesting that the observed sensorimotor and cognitive phenotypes are related to central nervous system processes. Indeed, measurements of hippocampal insulin receptor and glycogen synthase kinase-3β (GSK-3β) activation revealed a pattern similar to that obtained in the behavioral measurements while Akt activation presented a dominant effect of diet. HFD manipulation induced genotype-independent hyperlipidation of apoE, and reduced levels of brain apoE in apoE3 mice, rendering them similar to apoE4 mice, whose brain apoE levels were not affected by the diet. No such effect was observed in the peripheral plasma levels of apoE, suggesting that the pathological effects of apoE4 under the control diet and apoE3 under HFD conditions are related to the decreased levels of brain apoE. Taken together, our data suggests that diabetic mechanisms play an important role in mediating the pathological effects of apoE4 and that consequently, diabetic-related therapy may be useful in treating apoE4 pathology in AD.


Int J Mol Sci


Koren-Iton A,Salomon-Zimri S,Smolar A,Shavit-Stein E,Dori A,Chapman J,Michaelson DM




Has Abstract


2020-02-14 00:00:00










  • Chromatin structure following UV-induced DNA damage-repair or death?

    abstract::In eukaryotes, DNA is compacted into a complex structure known as chromatin. The unravelling of DNA is a crucial step in DNA repair, replication, transcription and recombination as this allows access to DNA for these processes. Failure to package DNA into the nucleosome, the individual unit of chromatin, can lead to g...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Farrell AW,Halliday GM,Lyons JG

    更新日期:2011-01-01 00:00:00

  • The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer.

    abstract::Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix components crucial for tumor growth, invasion and metastasis. MMPs are controlled by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). We and others have demonstrated that MMPs and TIMPs are espe...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Herszényi L,Hritz I,Lakatos G,Varga MZ,Tulassay Z

    更新日期:2012-10-16 00:00:00

  • Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids.

    abstract::Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Sakuma T,Takenaga M,Kawabe Y,Nakamura T,Kamihira M,Yamamoto T

    更新日期:2015-10-09 00:00:00

  • Leucine-Rich Repeat Kinase 2 Controls Inflammatory Cytokines Production through NF-κB Phosphorylation and Antigen Presentation in Bone Marrow-Derived Dendritic Cells.

    abstract::Leucine-rich repeat kinase 2 (LRRK2) is the causal molecule of familial Parkinson's disease. Although the characteristics of LRRK2 have gradually been revealed, its true physiological functions remain unknown. LRRK2 is highly expressed in immune cells such as B2 cells and macrophages, suggesting that it plays importan...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Kubo M,Nagashima R,Kurihara M,Kawakami F,Maekawa T,Eshima K,Ohta E,Kato H,Obata F

    更新日期:2020-03-10 00:00:00

  • Chemical constituents analysis and antidiabetic activity validation of four fern species from Taiwan.

    abstract::Pterosins are abundant in ferns, and pterosin A was considered a novel activator of adenosine monophosphate-activated protein kinase, which is crucial for regulating blood glucose homeostasis. However, the distribution of pterosins in different species of ferns from various places in Taiwan is currently unclear. To ad...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chen CY,Chiu FY,Lin Y,Huang WJ,Hsieh PS,Hsu FL

    更新日期:2015-01-22 00:00:00

  • Proteome Profile and Quantitative Proteomic Analysis of Buffalo (Bubalusbubalis) Follicular Fluid during Follicle Development.

    abstract::Follicular fluid (FF) accumulates in the antrum of the ovarian follicle and provides the microenvironment for oocyte development. FF plays an important role in follicle growth and oocyte maturation. The FF provides a unique window to investigate the processes occurring during buffalo follicular development. The observ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Fu Q,Huang Y,Wang Z,Chen F,Huang D,Lu Y,Liang X,Zhang M

    更新日期:2016-04-29 00:00:00

  • DNA2-An Important Player in DNA Damage Response or Just Another DNA Maintenance Protein?

    abstract::The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting wi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Pawłowska E,Szczepanska J,Blasiak J

    更新日期:2017-07-18 00:00:00

  • Effects of Single and Double Mutants in Human Glucose-6-Phosphate Dehydrogenase Variants Present in the Mexican Population: Biochemical and Structural Analysis.

    abstract::Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent human enzymopathy, affecting over 400 million people globally. Worldwide, 217 mutations have been reported at the genetic level, and only 19 have been found in Mexico. The objective of this work was to contribute to the knowledge of the function ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Martínez-Rosas V,Juárez-Cruz MV,Ramírez-Nava EJ,Hernández-Ochoa B,Morales-Luna L,González-Valdez A,Serrano-Posada H,Cárdenas-Rodríguez N,Ortiz-Ramírez P,Centeno-Leija S,Arreguin-Espinosa R,Cuevas-Cruz M,Ortega-Cuellar D,Pérez d

    更新日期:2020-04-15 00:00:00

  • mRNA and miRNA Profiles of Exosomes from Cultured Tumor Cells Reveal Biomarkers Specific for HPV16-Positive and HPV16-Negative Head and Neck Cancer.

    abstract::Human papillomavirus (HPV)(+) and HPV(-) head and neck cancer (HNC) cells' interactions with the host immune system are poorly understood. Recently, we identified molecular and functional differences in exosomes produced by HPV(+) vs. HPV(-) cells, suggesting that genetic cargos of exosomes might identify novel biomar...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Ludwig S,Sharma P,Wise P,Sposto R,Hollingshead D,Lamb J,Lang S,Fabbri M,Whiteside TL

    更新日期:2020-11-13 00:00:00

  • Impact of PPAR-Alpha Polymorphisms-The Case of Metabolic Disorders and Atherosclerosis.

    abstract::Peroxisome proliferator activated receptor α (PPARα) has the most relevant biological functions among PPARs. Activation by drugs and dietary components lead to major metabolic changes, from reduced triglyceridemia to improvement in the metabolic syndrome. Polymorphisms of PPARα are of interest in order to improve our ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ruscica M,Busnelli M,Runfola E,Corsini A,Sirtori CR

    更新日期:2019-09-06 00:00:00

  • Cardiotonic Steroids-A Possible Link Between High-Salt Diet and Organ Damage.

    abstract::High dietary salt intake has been listed among the top ten risk factors for disability-adjusted life years. We discuss the role of endogenous cardiotonic steroids in mediating the dietary salt-induced hypertension and organ damage. ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Paczula A,Wiecek A,Piecha G

    更新日期:2019-01-30 00:00:00

  • Increased Urinary 3-Mercaptolactate Excretion and Enhanced Passive Systemic Anaphylaxis in Mice Lacking Mercaptopyruvate Sulfurtransferase, a Model of Mercaptolactate-Cysteine Disulfiduria.

    abstract::Mercaptopyruvate sulfurtransferase (Mpst) and its homolog thiosulfate sulfurtransferase (Tst = rhodanese) detoxify cyanide to thiocyanate. Mpst is attracting attention as one of the four endogenous hydrogen sulfide (H2S)/reactive sulfur species (RSS)-producing enzymes, along with cystathionine β-synthase (Cbs), cystat...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Akahoshi N,Minakawa T,Miyashita M,Sugiyama U,Saito C,Takemoto R,Honda A,Kamichatani W,Kamata S,Anan Y,Ishii I

    更新日期:2020-01-27 00:00:00

  • Uncovering the properties of energy-weighted conformation space networks with a hydrophobic-hydrophilic model.

    abstract::The conformation spaces generated by short hydrophobic-hydrophilic (HP) lattice chains are mapped to conformation space networks (CSNs). The vertices (nodes) of the network are the conformations and the links are the transitions between them. It has been found that these networks have "small-world" properties without ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Lai Z,Su J,Chen W,Wang C

    更新日期:2009-04-21 00:00:00

  • The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich's Ataxia.

    abstract::Friedreich's ataxia (FA) is a trinucleotide repeats expansion neurodegenerative disorder, for which no cure or approved therapies are present. In most cases, GAA trinucleotide repetitions in the first intron of the FXN gene are the genetic trigger of FA, determining a strong reduction of frataxin, a mitochondrial prot...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: La Rosa P,Bertini ES,Piemonte F

    更新日期:2020-01-30 00:00:00

  • Cytomegalovirus Infections after Hematopoietic Stem Cell Transplantation: Current Status and Future Immunotherapy.

    abstract::Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Cho SY,Lee DG,Kim HJ

    更新日期:2019-05-30 00:00:00

  • Apelin Controls Angiogenesis-Dependent Glioblastoma Growth.

    abstract::Glioblastoma (GBM) present with an abundant and aberrant tumor neo-vasculature. While rapid growth of solid tumors depends on the initiation of tumor angiogenesis, GBM also progress by infiltrative growth and vascular co-option. The angiogenic factor apelin (APLN) and its receptor (APLNR) are upregulated in GBM patien...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Frisch A,Kälin S,Monk R,Radke J,Heppner FL,Kälin RE

    更新日期:2020-06-11 00:00:00

  • Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults.

    abstract::Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especiall...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Bellastella G,Maiorino MI,Longo M,Cirillo P,Scappaticcio L,Vietri MT,Bellastella A,Esposito K,De Bellis A

    更新日期:2020-02-19 00:00:00

  • Vortioxetine Subchronically Activates Serotonergic Transmission via Desensitization of Serotonin 5-HT1A Receptor with 5-HT3 Receptor Inhibition in Rats.

    abstract::Vortioxetine is a novel, multimodal antidepressant with unique targets, including the inhibition of the serotonin transporter (SET), of serotonin 5-HT3 (5-HT3R), and of 5-HT7 (5-HT7R) receptors and partial agonism to serotonin 5-HT1A (5-HT1AR) receptors in humans. Vortioxetine has a lower affinity to 5-HT1AR and 5-HT7...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Okada M,Okubo R,Fukuyama K

    更新日期:2019-12-10 00:00:00

  • Icariin Regulates Cellular Functions and Gene Expression of Osteoarthritis Patient-Derived Human Fibroblast-Like Synoviocytes.

    abstract::Synovial inflammation plays an important role in the pathogenesis and progress of osteoarthritis (OA). There is an urgent need to find safe and effective drugs that can reduce the inflammation and regulate the pathogenesis of cytokines of the OA disease. Here, we investigated the effect of icariin, the major pharmacol...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Pan L,Zhang Y,Chen N,Yang L

    更新日期:2017-12-08 00:00:00

  • Exploration of Binding Mechanism of a Potential Streptococcus pneumoniae Neuraminidase Inhibitor from Herbaceous Plants by Molecular Simulation.

    abstract::Streptococcus pneumoniae can cause diseases such as pneumonia. Broad-spectrum antibiotic therapy for Streptococcus pneumoniae is increasingly limited due to the emergence of drug-resistant strains. The development of novel drugs is still currently of focus. Abundant polyphenols have been demonstrated to have antivirus...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Guan S,Zhu K,Dong Y,Li H,Yang S,Wang S,Shan Y

    更新日期:2020-02-03 00:00:00

  • Assessment of the Efficacy of Platelet-Rich Plasma in the Treatment of Traumatic Canine Fractures.

    abstract::The role of platelet-rich plasma (PRP) in promoting the healing of bone fractures has not yet been clearly stated. The aim of this prospective clinical study was to evaluate the effectiveness of plasma rich in growth factors (PRGF, a PRP derivate) in the treatment of naturally-occurring bone fractures in dogs. With th...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: López S,Vilar JM,Sopena JJ,Damià E,Chicharro D,Carrillo JM,Cuervo B,Rubio AM

    更新日期:2019-03-01 00:00:00

  • Distinct Carbon and Nitrogen Metabolism of Two Contrasting Poplar Species in Response to Different N Supply Levels.

    abstract::Poplars have evolved various strategies to optimize acclimation responses to environmental conditions. However, how poplars balance growth and nitrogen deficiency remains to be elucidated. In the present study, changes in root development, carbon and nitrogen physiology, and the transcript abundance of associated gene...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Meng S,Wang S,Quan J,Su W,Lian C,Wang D,Xia X,Yin W

    更新日期:2018-08-06 00:00:00

  • Clouded Issues for PHACTR1.

    abstract::I have read with interest the recent paper by Han and coworkers on the putative effects of a PHACTR1 variant in the context of coronary artery disease. The authors conclude to a significant risk-enhancing role of rs12526453 on the grounds of 19 earlier case-control studies. ...

    journal_title:International journal of molecular sciences

    pub_type: 评论,杂志文章


    authors: Sand PG

    更新日期:2015-04-29 00:00:00

  • Biochemical properties and potential applications of recombinant leucine aminopeptidase from Bacillus kaustophilus CCRC 11223.

    abstract::Experiments were carried out to investigate the effects of various factors on the activity and conformation of recombinant leucine aminopeptidase of Bacillus kaustophilus CCRC 11223 (BkLAP) and potential utilization of BkLAP in the hydrolysis of anchovy protein. Optimal temperature and pH of BkLAP were 70 °C and 8.0 i...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Shen Y,Wang F,Lan D,Liu Y,Yang B,Wang Y

    更新日期:2011-01-01 00:00:00

  • A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives.

    abstract::Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75NTR) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, an...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Sánchez-Sánchez J,Arévalo JC

    更新日期:2017-03-14 00:00:00

  • The Effect of the Chorion on Size-Dependent Acute Toxicity and Underlying Mechanisms of Amine-Modified Silver Nanoparticles in Zebrafish Embryos.

    abstract::As the worldwide application of nanomaterials in commercial products increases every year, various nanoparticles from industry might present possible risks to aquatic systems and human health. Presently, there are many unknowns about the toxic effects of nanomaterials, especially because the unique physicochemical pro...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chen ZY,Li NJ,Cheng FY,Hsueh JF,Huang CC,Lu FI,Fu TF,Yan SJ,Lee YH,Wang YJ

    更新日期:2020-04-20 00:00:00

  • Optimization of a WGA-Free Molecular Tagging-Based NGS Protocol for CTCs Mutational Profiling.

    abstract::Molecular characterization of Circulating Tumor Cells (CTCs) is still challenging, despite attempts to minimize the drawbacks of Whole Genome Amplification (WGA). In this paper, we propose a Next-Generation Sequencing (NGS) optimized protocol based on molecular tagging technology, in order to detect CTCs mutations whi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: De Luca G,Cardinali B,Del Mastro L,Lastraioli S,Carli F,Ferrarini M,Calin GA,Garuti A,Mazzitelli C,Zupo S,Dono M

    更新日期:2020-06-19 00:00:00

  • AMP-Activated Protein Kinase as a Reprogramming Strategy for Hypertension and Kidney Disease of Developmental Origin.

    abstract::Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming proce...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Tain YL,Hsu CN

    更新日期:2018-06-12 00:00:00

  • Applications and mechanisms of ionic liquids in whole-cell biotransformation.

    abstract::Ionic liquids (ILs), entirely composed of cations and anions, are liquid solvents at room temperature. They are interesting due to their low vapor pressure, high polarity and thermostability, and also for the possibility to fine-tune their physicochemical properties through modification of the chemical structures of t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Fan LL,Li HJ,Chen QH

    更新日期:2014-07-09 00:00:00

  • Expression of selected Ginkgo biloba heat shock protein genes after cold treatment could be induced by other abiotic stress.

    abstract::Heat shock proteins (HSPs) play various stress-protective roles in plants. In this study, three HSP genes were isolated from a suppression subtractive hybridization (SSH) cDNA library of Ginkgo biloba leaves treated with cold stress. Based on the molecular weight, the three genes were designated GbHSP16.8, GbHSP17 and...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Cao F,Cheng H,Cheng S,Li L,Xu F,Yu W,Yuan H

    更新日期:2012-01-01 00:00:00