Abstract:
:Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism-accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Rozpędek-Kamińska W,Siwecka N,Wawrzynkiewicz A,Wojtczak R,Pytel D,Diehl JA,Majsterek Idoi
10.3390/ijms21062108subject
Has Abstractpub_date
2020-03-19 00:00:00issue
6issn
1422-0067pii
ijms21062108journal_volume
21pub_type
杂志文章,评审abstract::Epidemiological studies on workers employed at the Mayak plutonium enrichment plant have demonstrated an association between external gamma ray exposure and an elevated risk of ischemic heart disease (IHD). In a previous study using fresh-frozen post mortem samples of the cardiac left ventricle of Mayak workers and no...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21186832
更新日期:2020-09-17 00:00:00
abstract::In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18040810
更新日期:2017-04-12 00:00:00
abstract::We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlatio...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20205053
更新日期:2019-10-11 00:00:00
abstract::Since 2003, several loss-of-function mutations in the HCN4 gene, which encodes the HCN4 protein, have been associated with sinus node dysfunction. In human sinoatrial node (SAN), HCN4 is the most abundant of the four isoforms of the HCN family. Tetramers of HCN subunits constitute the ion channels that conduct the hyp...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms16023071
更新日期:2015-01-29 00:00:00
abstract::Polygalacturonase (PG), a large hydrolase family in plants, is involved in pectin disassembly of the cell wall in plants. The present study aims to characterize PG genes and investigate their expression patterns in Solanum lycopersicum. We identified 54 PG genes in the tomato genome and compared their amino acid seque...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19082290
更新日期:2018-08-04 00:00:00
abstract::A small gram-negative bacterium, Coxiella burnetii (C. burnetii), is responsible for a zoonosis called Q fever. C. burnetii is an intracellular bacterium that can survive inside microbicidal cells like monocytes and macrophages by hijacking several functions of the immune system. Among several virulence factors, the l...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18122509
更新日期:2017-11-23 00:00:00
abstract::ABA is involved in plant responses to a broad range of pathogens and exhibits complex antagonistic and synergistic relationships with salicylic acid (SA) and ethylene (ET) signaling pathways, respectively. However, the specific receptor of ABA that triggers the positive and negative responses of ABA during immune resp...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21165852
更新日期:2020-08-14 00:00:00
abstract::For possible future use in Photodynamic Therapy (PDT) and/or Photothermal Therapy (PTT) of cancer and screening of cancer cells a new type of ionic liquid photosensitizer -Cholinium-Purpurin-18 (Chol-Pu-18) - was synthesized and small gold (Au) nanoparticles, stabilized by this photosensitizer were prepared without ad...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms9050864
更新日期:2008-05-01 00:00:00
abstract::A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE) inhibition assay in vitro. Compounds M2, M4,...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms140817193
更新日期:2013-08-20 00:00:00
abstract::Wound healing is a multistep process with four overlapping but distinct stages: hemostasis, inflammation, proliferation, and remodeling. An alteration at any stage may lead to the development of chronic non-healing wounds or excessive scar formation. Impaired wound healing presents a significant health and economic bu...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19103217
更新日期:2018-10-18 00:00:00
abstract::An acylated flavonol glycoside, helichrysoside, at a dose of 10 mg/kg/day per os for 14 days, improved the glucose tolerance in mice without affecting the food intake, visceral fat weight, liver weight, and other plasma parameters. In this study, using hepatoblastoma-derived HepG2 cells, helichrysoside, trans-tilirosi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20246322
更新日期:2019-12-14 00:00:00
abstract::The let-7 family is the second microRNA found in C. elegans. Recent researches have found it is highly expressed in the cardiovascular system. Studies have revealed the aberrant expression of let-7 members in cardiovascular diseases, such as heart hypertrophy, cardiac fibrosis, dilated cardiomyopathy (DCM), myocardial...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms141123086
更新日期:2013-11-21 00:00:00
abstract::Although poly(2-hydroxyethyl methacrylate) (pHEMA) and polyethylene glycol methacrylate (PEGMA) have been demonstrated to inhibit bacterial adhesion, no study has compared antibacterial adhesion when salivary pellicle is coated on polymethyl methacrylate (PMMA) grafted with pHEMA and on PMMA grafted with PEGMA. In thi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19092764
更新日期:2018-09-14 00:00:00
abstract::The use of herbicides is an effective and economic way to control weeds, but their availability for rapeseed is limited due to the shortage of herbicide-resistant cultivars in China. The single-point mutation in the acetohydroxyacidsynthase (AHAS) gene can lead to AHAS-inhibiting herbicide resistance. In this study, t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21041345
更新日期:2020-02-17 00:00:00
abstract::Polyphenol compositions and concentrations in skins and seeds of five muscadine grapes (cv. "Noble", "Alachua", "Carlos", "Fry", and "Granny Val") cultivated in the United States (Tallahassee-Florida, TA-FL) and South China (Nanning-Guangxi, NN-GX and Pu'er-Yunnan, PE-YN) were investigated, using ultra performance liq...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18030631
更新日期:2017-03-14 00:00:00
abstract::Genomic DNA is constantly damaged by factors produced during natural metabolic processes as well as agents coming from the external environment. Considering such a wide array of damaging agents, eukaryotic cells have evolved a DNA damage response (DRR) that opposes the influence of deleterious factors. Despite the bro...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21113934
更新日期:2020-05-30 00:00:00
abstract::Interleukin (IL)-4 and -13 are structurally and functionally related cytokines sharing common receptor subunits. They regulate immune responses and, moreover, are involved in the pathogenesis of a variety of human neoplasms. Three different receptors have been described for IL-4, but only IL-4 receptor type II (IL-4Rα...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms22020727
更新日期:2021-01-13 00:00:00
abstract::MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the poss...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22031105
更新日期:2021-01-22 00:00:00
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
doi:10.3390/ijms21030916
更新日期:2020-01-30 00:00:00
abstract::Cancers can cause some proteins to be aberrantly excreted or released in the urine, which can be used as biomarkers. To screen for potential biomarkers for endometrial cancer (ECa), the urinary proteins from patients who were newly diagnosed with early stage ECa and untreated controls were separated using two-dimensio...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13089489
更新日期:2012-01-01 00:00:00
abstract::The voltage-dependent anion channel (VDAC), a highly conserved major mitochondrial outer membrane protein, plays crucial roles in energy metabolism and metabolite transport. However, knowledge about the roles of the VDAC family in plants is limited. In this study, we investigated the expression pattern of VDAC1 in Ara...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms14010701
更新日期:2013-01-04 00:00:00
abstract::This study aimed at the characterization of the antioxidant power of polyphenol extracts (PE) obtained from the algae Cystoseira foeniculacea (CYS) (Phaeophyta) and from the halophyte Halocnemum strobilaceum (HAL), growing in the solar saltworks of western Sicily (Italy), and at the evaluation of their anti-microfouli...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20040881
更新日期:2019-02-18 00:00:00
abstract::The ATP-sensitive K+ channel (KATP) is involved in hypersensitivity during chronic pain and is presumed to be a downstream target of mu opioid receptors. Multiple subtypes of KATP channels exist in the peripheral and central nervous system and their activity may be inversely correlated to chronic pain phenotypes in ro...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20092251
更新日期:2019-05-07 00:00:00
abstract::Previously, we demonstrated that the immediate administration of multitarget anxiolytic afobazole slows down the progression of neuronal damage in a 6-hydroxidodamine (6-OHDA) model of Parkinson's disease due to the activation of chaperone Sigma1R. The aim of the present study is to evaluate the therapeutic potential ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21207620
更新日期:2020-10-15 00:00:00
abstract::Recent studies have shown that plumbagin has anti-inflammatory, anti-allergic, antibacterial, and anti-cancer activities; however, it has not yet been shown whether plumbagin suppresses alpha-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis to prevent hyperpigmentation. In this study, we demonstrated t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18020320
更新日期:2017-02-03 00:00:00
abstract::The retromer is a multiprotein complex conserved from yeast to humans, which is involved in intracellular protein trafficking and protein recycling. Selection of cargo proteins transported by the retromer depends on the core retromer subunit composed of the three vacuolar protein sorting (VPS) proteins, namely VPS26, ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20020362
更新日期:2019-01-16 00:00:00
abstract::Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent protein lysine modifying enzymes. They are key regulators for a wide variety of cellular and physiological processes such as cell proliferation, differentiation, DNA damage and stress response, genome stability, cell survival, ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20194945
更新日期:2019-10-07 00:00:00
abstract::In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten (Fumonisin B(1), FB(1)) was coupled to ovalbumin (OVA) and bovine serum albumin (BSA), respectively by a short cross-linker reagent (glutaraldehyde, GA). T...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms13010084
更新日期:2012-01-01 00:00:00
abstract::This paper explores the effect of granulocyte colony-stimulating factor (G-CSF) on mouse myocardial microvascular endothelial cell (CMECs) proliferation. CMECs were harvested from C57/BL6 mice. CMECs were cultured in medium containing G-CSF (0 ng/mL, 20 ng/mL, 40 ng/mL, 60 ng/mL) for five days. Proliferative activity ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms12021306
更新日期:2011-02-22 00:00:00
abstract::A three-dimensional (3D) representative volume element (RVE) model was developed for analyzing effective mechanical behavior of fiber-reinforced ceramic matrix composites with imperfect interfaces. In the model, the fiber is assumed to be perfectly elastic until its tensile strength, and the ceramic material is modele...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms151223389
更新日期:2014-12-16 00:00:00