Abstract：
:Cytoplasmic aggregates and nuclear depletion of the ubiquitous RNA-binding protein TDP-43 have been described in the autoptic brain tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTLD) patients and both TDP-43 loss-of-function and gain-of-function mechanisms seem to contribute to the neurodegenerative process. Among the wide array of RNA targets, TDP-43 regulates progranulin (GRN) mRNA stability and sortilin (SORT1) splicing. Progranulin is a secreted neurotrophic and neuro-immunomodulatory factor whose endocytosis and delivery to the lysosomes are regulated by the neuronal receptor sortilin. Moreover, GRN loss-of-function mutations are causative of a subset of FTLD cases showing TDP-43 pathological aggregates. Here we show that TDP-43 loss-of-function differently affects the progranulin-sortilin axis in murine and human neuronal cell models. We demonstrated that although TDP-43 binding to GRN mRNA occurs similarly in human and murine cells, upon TDP-43 depletion, a different control of sortilin splicing and protein content may determine changes in extracellular progranulin uptake that account for increased or unchanged secreted protein in murine and human cells, respectively. As targeting the progranulin-sortilin axis has been proposed as a therapeutic approach for GRN-FTLD patients, the inter-species differences in TDP-43-mediated regulation of this pathway must be considered when translating studies from animal models to patients.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Gumina V,Onesto E,Colombrita C,Maraschi A,Silani V,Ratti Adoi
10.3390/ijms20235866subject
Has Abstractpub_date
2019-11-22 00:00:00issue
23issn
1422-0067pii
ijms20235866journal_volume
20pub_type
杂志文章abstract：:Early-life adversity may have programming effects on neuroendocrine and immune adaptation mechanisms in humans and socially living animals. Using a pig model, we investigated the effect of daily 2-h maternal and littermate deprivation from postnatal days 2-15, either alone (DA) or in a group of littermates (DG) on the...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21155212
更新日期：2020-07-23 00:00:00
abstract：BACKGROUND:Research evidence indicates that vitamin D deficiency is involved in the pathogenesis of insulin resistance (IR) and associated metabolic disorders including hyperglycemia and dyslipidemia. It also suggested that vitamin D deficiency is associated with elevated levels of oxidative stress and its complication...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,随机对照试验
doi：10.3390/ijms20122891
更新日期：2019-06-13 00:00:00
abstract：:Atrazine, a member of the 2-chloro-s-triazine family of herbicides, is the most widely used pesticide in the world and often detected in agriculture watersheds. Although it was generally considered as an endocrine disruptor, posing a potential threat to human health, the molecular mechanisms of atrazine effects remain...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms151017806
更新日期：2014-10-01 00:00:00
abstract：:The present study was undertaken to develop a rat model for monitoring the early development of breast cancer. Twelve female rats were divided into two groups of six rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer or with bacterial lipopolysaccharide to induce inflammation. Serum samp...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms12021030
更新日期：2011-02-07 00:00:00
abstract：:Mucin1 (MUC1) is a highly glycosylated transmembrane protein that plays a crucial role in the lubrication and protection of normal epithelial cells. However, MUC1 has emerged as a potential target for cancer therapy because it is overexpressed and functions in several types of cancers. Recently, we produced a monoclon...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19072004
更新日期：2018-07-09 00:00:00
abstract：:We have previously reported that adipose tissue-derived stem cells (ASCs) cultured at high cell density can induce cancer cell death through the expression of type I interferons and tumor necrosis factor (TNF)-related apoptosis-inducing ligands (TRAIL). Here, we investigated whether TRAIL-expressing ASCs induced by M1...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21113887
更新日期：2020-05-29 00:00:00
abstract：:Blood vessels in vertebrates are established and genetically controlled in an evolutionarily-conserved manner during embryogenesis. Disruption of vascular growth by chemical compounds or environmental hormones may cause developmental defects. This study analyzed the vascular impacts of marine compound GB9 in zebrafish...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18081696
更新日期：2017-08-03 00:00:00
abstract：:Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions. The study of bone diseases characterized by increased or reduced bone mass due to osteoclast alterations has been essential to understand the great rol...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20184502
更新日期：2019-09-11 00:00:00
abstract：:Sex reversal has been used as a breeding strategy by salmonid fish to produce genetically and phenotypically single sex populations. Production of all-female fish has great importance for the creation of monosex female triploids of salmonid fish, which are valued for their sterility, lack of female maturation, and lar...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms22020964
更新日期：2021-01-19 00:00:00
abstract：:Cells have evolved balanced systems that ensure an appropriate response to stress. The systems elicit repair responses in temporary or moderate stress but eliminate irreparable cells via apoptosis in detrimental conditions of prolonged or severe stress. The tumor suppressor p53 is a central player in these stress resp...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20205179
更新日期：2019-10-18 00:00:00
abstract：:Panicle degeneration, also known as panicle abortion, is a serious defect and causes heavy losses to reproductive yield in cereals. Several mutants have been reported to display the phenotype of spikelet abortion in rice. Recent findings have resulted in significant breakthroughs, but comprehensive understanding about...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20071613
更新日期：2019-04-01 00:00:00
abstract：:There is strong evidence that exposure to fine particulate matter (PM2.5) and a high-fat diet (HFD) increase the risk of mortality from atherosclerotic cardiovascular diseases. Recent studies indicate that PM2.5 generated by combustion activates the Aryl Hydrocarbon Receptor (AHR) and inflammatory cytokines contributi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21218287
更新日期：2020-11-05 00:00:00
abstract：:The local anesthetic lidocaine, which has been used extensively during liposuction, has been reported to have cytotoxic effects and therefore would be unsuitable for use in autologous lipotransfer. We evaluated the effect of lidocaine on the distribution, number, and viability of adipose-derived stem cells (ASCs), pre...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21082869
更新日期：2020-04-20 00:00:00
abstract：:Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteine...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms15046391
更新日期：2014-04-15 00:00:00
abstract：:Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged i...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21124269
更新日期：2020-06-16 00:00:00
abstract：:Calmodulin (CaM) is the principal Ca2+ sensor in eukaryotic cells, orchestrating the activity of hundreds of proteins. Disease causing mutations at any of the three genes that encode identical CaM proteins lead to major cardiac dysfunction, revealing the importance in the regulation of excitability. In turn, some muta...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20020400
更新日期：2019-01-18 00:00:00
abstract：:p-Coumalic acid (PCA), caffeic acid (CA), gallic acid (GA) and chlorogenic acid (CGA) are the major phenolic acids that co-exist with soy protein components in foodstuffs. Surprisingly, there are only a handful of reports that describe their interaction with β-Conglycinin (7S), a major soy protein. In this report, we ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17101671
更新日期：2016-10-02 00:00:00
abstract：:Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease caused by an unstable cardiotocography (CTG) repeat expansion in the DMPK gene. This disease is characterized by high clinical and genetic variability, leading to some difficulties in the diagnosis and prognosis of DM1. Better understanding the origin ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21020457
更新日期：2020-01-10 00:00:00
abstract：:Patients with advanced skeletal metastases arising from primary cancers including breast, lung, and prostate suffer from extreme pain, bone loss, and frequent fractures. While the importance of interactions between bone and tumors is well-established, our understanding of complex cell-cell and cell-microenvironment in...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21186913
更新日期：2020-09-21 00:00:00
abstract：:We have reported that conventional protein kinase Cγ (cPKCγ)-modulated neuron-specific autophagy improved the neurological outcome of mice following ischemic stroke through the Akt-mechanistic target of rapamycin (mTOR) pathway. However, its detailed molecular mechanism remains unclear. In this study, prim...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19051380
更新日期：2018-05-06 00:00:00
abstract：:Hepatocyte cell death is a key process in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the factors responsible for and mechanisms underlying NASH-related cell death have not yet been elucidated in detail. We herein investigated the effects of intracellular glyceraldehyde (GA)-derived advanced glyc...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21144861
更新日期：2020-07-09 00:00:00
abstract：:Electronegative low-density lipoprotein (LDL(-)) is a minor modified LDL subfraction that is present in blood. LDL(-) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is co...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms14022601
更新日期：2013-01-28 00:00:00
abstract：:Before utilization in biomedical diagnosis, therapeutic treatment, and biotechnology, the diverse variety of peptides and proteins must be preliminarily purified and thoroughly characterized. The recombinant DNA technology and heterologous protein expression have helped simplify the isolation of targeted polypeptides ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21030928
更新日期：2020-01-31 00:00:00
abstract：:Liver injuries caused by the use of exogenous compounds such as drugs, herbs, and alcohol are commonly well diagnosed using laboratory tests, toxin analyses, or eventually reactive intermediates generated during metabolic degradation of the respective chemical in the liver and subject to covalent binding by target pro...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21010212
更新日期：2019-12-27 00:00:00
abstract：:Melatonin is a pleiotropic molecule with many cellular and systemic actions, including chronobiotic effects. Beneficial effects are widely documented concerning the treatment of neoplastic diseases in vivo as well as reductions in viability of cultured cells from melanoma, one of the most aggressive cancers in humans....
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms14023901
更新日期：2013-02-14 00:00:00
abstract：:Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms160921215
更新日期：2015-09-07 00:00:00
abstract：:Amino acid transporters alanine-serine-cysteine transporter 2 (ASCT2) and L-Type Amino Acid Transporter 1 (LAT1) are coordinately enhanced in human cancers where among other roles, they are thought to drive mechanistic target-of-rapamycin (mTOR) growth signaling. To assess ASCT2 and LAT1 as therapeutic targets, nine u...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19072093
更新日期：2018-07-19 00:00:00
abstract：:Lung cancer is the leading cause of death for malignancy worldwide. Its molecular profiling has enriched our understanding of cancer initiation and progression and has become fundamental to provide guidance on treatment with targeted therapies. Testing the presence of driver mutations in specific genes in lung tumors ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms22020612
更新日期：2021-01-09 00:00:00
abstract：:CDK5RAP3 was regarded as the most significant regulator of cellular responses against heat stress, which is associated with dysfunctions of the immune system and animal susceptibility to disease. Despite this, little known about how CDK5RAP3 regulates heat stress response. In this study, CDK5RAP3 conditional Knockout ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21218400
更新日期：2020-11-09 00:00:00
abstract：:In this study, nanoparticle-incorporated nanofiber-covered yarns were prepared using a custom-made needle-free electrospinning system. The ultimate goal of this work was to prepare functional nanofibrous surfaces with antibacterial properties and realize high-speed production. As antibacterial agents, we used various ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20174317
更新日期：2019-09-03 00:00:00
