Abstract：
:Astrocytic dysfunction has been implicated in Parkinson's disease (PD) pathogenesis. While the Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 signaling axis is known to play a role in PD-like neuropathology, the molecular mechanisms that govern this process remain poorly understood. Herein, we show that TWEAK levels are elevated in PD serum compared to controls. Moreover, using both U373 human astrocyte cells and primary mouse astrocytes, we demonstrate that TWEAK induces mitochondrial oxidative stress as well as protein kinase C delta (PKCδ) and signal transducer and activator of transcription 3 (STAT3) activation, accompanied by NLRC4 inflammasome activation and upregulation and release of proinflammatory cytokines, including IL-1β, TNF-α, and IL-18. Mechanistically, TWEAK-induced PKCδ activation enhances the STAT3/NLRC4 signaling pathway and other proinflammatory mediators through a mitochondrial oxidative stress-dependent mechanism. We further show that PKCδ knockdown and mito-apocynin, a mitochondrial antioxidant, suppress TWEAK-induced proinflammatory NLRC4/STAT3 signaling and cellular oxidative stress response. Notably, we validated our in vitro findings in an MPTP mouse model of PD and in mice receiving intrastriatal administration of TWEAK. These results indicate that TWEAK is a key regulator of astroglial reactivity and illustrate a novel mechanism by which mitochondrial oxidative stress may influence dopaminergic neuronal survival in PD.
journal_name
Cellsjournal_title
Cellsauthors
Samidurai M,Tarale P,Janarthanam C,Estrada CG,Gordon R,Zenitsky G,Jin H,Anantharam V,Kanthasamy AG,Kanthasamy Adoi
10.3390/cells9081831subject
Has Abstractpub_date
2020-08-04 00:00:00issue
8issn
2073-4409pii
cells9081831journal_volume
9pub_type
杂志文章相关文献
Cells文献大全abstract：:The aim of this review is to outline emerging biomarkers that can serve as early diagnostic tools to identify patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and, among them, the subgroup of best candidates for clinical trials on emerging compounds. Regarding possible pre...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9041005
更新日期：2020-04-17 00:00:00
abstract：:CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α') and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells10010181
更新日期：2021-01-18 00:00:00
abstract：:The Hippo signaling pathway is involved in tissue size regulation and tumorigenesis. Genetic deletion or aberrant expression of some Hippo pathway genes lead to enhanced cell proliferation, tumorigenesis, and cancer metastasis. Recently, multiple studies have identified a wide range of upstream regulators of the Hippo...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8050426
更新日期：2019-05-08 00:00:00
abstract：:Mitotic spindles are highly organized, microtubule (MT)-based, transient structures that serve the fundamental function of unerring chromosome segregation during cell division and thus of genomic stability during tissue morphogenesis and homeostasis. Hence, a multitude of MT-associated proteins (MAPs) regulates the dy...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9112348
更新日期：2020-10-23 00:00:00
abstract：:The PIKfyve inhibitor apilimod is currently undergoing clinical trials for treatment of COVID-19. However, although apilimod might prevent viral invasion by inhibiting host cell proteases, the same proteases are critical for antigen presentation leading to T cell activation and there is good evidence from both in vitr...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells10010030
更新日期：2020-12-27 00:00:00
abstract：:Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the path...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9081899
更新日期：2020-08-13 00:00:00
abstract：:Growth factors are important regulators during organ development. For many vertebrates (but not humans) it is known how they contribute to the formation and expansion of PDX1-positive cells during pancreas organogenesis. Here, the effects of the fibroblast growth factors FGF2, FGF7, FGF10, and epidermal growth factor ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9091927
更新日期：2020-08-20 00:00:00
abstract：:The transient receptor potential cation channel subfamily M member 4 (TRPM4) channel influences calcium homeostasis during many physiological activities such as insulin secretion, immune response, respiratory reaction, and cerebral vasoconstriction. This calcium-activated, monovalent, selective cation channel also pla...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells7060062
更新日期：2018-06-15 00:00:00
abstract：:Nitric oxide (NO) is an important mediator of inflammation response and the production of NO has been linked to a variety of diseases, including tumors, inflammation and central nervous system diseases. In macrophages, a high level of NO is generated by iNOS during inflammatory responses triggered by cytokines or path...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8101255
更新日期：2019-10-15 00:00:00
abstract：:: In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs-melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these-at first sight-dissimilar cancer types, we aim at...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9010114
更新日期：2020-01-02 00:00:00
abstract：:The role of small, non-coding microRNAs (miRNAs) has recently emerged as fundamental in the regulation of the physiology of the cardiovascular system. Several specific miRNAs were found to be expressed in embryonic, postnatal, and adult cardiac tissues. In the present review, we will provide an overview about their ro...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells3030802
更新日期：2014-08-05 00:00:00
abstract：:The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaini...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9071678
更新日期：2020-07-13 00:00:00
abstract：:Nile tilapia is the third most cultivated fish worldwide and a novel model species for evolutionary studies. Aiming to improve productivity and contribute to the selection of traits of economic impact, biotechnological approaches have been intensively applied to species enhancement. In this sense, recent studies have ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9081752
更新日期：2020-07-22 00:00:00
abstract：:The human gut relies on several cellular and molecular mechanisms to allow for an intact and dynamical intestinal barrier. Normally, only small amounts of luminal content pass the mucosa, however, if the control is broken it can lead to enhanced passage, which might damage the mucosa, leading to pathological condition...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8020193
更新日期：2019-02-22 00:00:00
abstract：:Glioblastoma (GBM) is one of the most intransigent and aggressive brain tumors, and its treatment is extremely challenging and ineffective. To improve patients' expectancy and quality of life, new therapeutic approaches were investigated. Melatonin is an endogenous indoleamine with an incredible variety of properties....
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9030599
更新日期：2020-03-03 00:00:00
abstract：:T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to deregulated cell gro...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9071726
更新日期：2020-07-18 00:00:00
abstract：:A new epoch is emerging with intense research on nutraceuticals, i.e., "food or food product that provides medical or health benefits including the prevention and treatment of diseases", such as Alzheimer's disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuropro...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9112347
更新日期：2020-10-23 00:00:00
abstract：:Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death and is the most common type of liver cancer. Due to the current paucity of drugs for HCC therapy there is a pressing need to develop new therapeutic concepts. In recent years, the role of Serum Response Factor (SRF) and its coactivator...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9122540
更新日期：2020-11-25 00:00:00
abstract：:Successful RNAi applications depend on strategies allowing stable and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. In this study, we proposed an endogenous microRNA (miRNA) cluster as a novel integration site for small hairpin RNAs (shRNAs). We successfully in...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8020113
更新日期：2019-02-01 00:00:00
abstract：:There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) ...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8121605
更新日期：2019-12-11 00:00:00
abstract：:Carnosine (β-alanyl-L-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Carnosine is involved in cellular defense mechanisms against oxidative stress, including the inhibition of amyloid-beta (Aβ) aggregation and the scavenging of reactive species...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8010064
更新日期：2019-01-17 00:00:00
abstract：:Increasing evidence suggests that metabolic alterations may be etiologically linked to neurodegenerative disorders such as Parkinson's disease (PD) and in particular empathizes the possibility of targeting mitochondrial dysfunctions to improve PD progression. Under different pathological conditions (i.e., cardiac and ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9092037
更新日期：2020-09-06 00:00:00
abstract：:Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in p...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9010060
更新日期：2019-12-24 00:00:00
abstract：:Transient receptor potential canonical 6 (TRPC6) is a cation selective, DAG-regulated, Ca2+-permeable channel activated by the agonists of Gq-protein-coupled heptahelical receptors. Dysfunctions of TRPC6 are implicated in the pathogenesis of various cardiovascular and kidney conditions such as vasospasm and glomerulos...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells3020247
更新日期：2014-04-04 00:00:00
abstract：:Multipotent adult mesenchymal stromal cells (MSCs) could represent an elegant source for the generation of patient-specific cardiomyocytes needed for regenerative medicine, cardiovascular research, and pharmacological studies. However, the differentiation of adult MSC into a cardiac lineage is challenging compared to ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020504
更新日期：2020-02-22 00:00:00
abstract：:Genetic disorders associated with metal metabolism form a large group of disorders and mostly result from defects in the proteins/enzymes involved in nutrient metabolism and energy production. These defects can affect different metabolic pathways and cause mild to severe disorders related to metal metabolism. Some dis...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8121598
更新日期：2019-12-09 00:00:00
abstract：:The maternal nutritional status is essential to the health and well-being of the fetus. Maternal protein restriction during the perinatal stage causes sperm alterations in the offspring that are associated with epididymal dysfunctions. Vascular endothelial growth factor (VEGF) and its receptor, VEGFr-2, as well as aqu...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8091094
更新日期：2019-09-17 00:00:00
abstract：:The Drosophila ovary offers a suitable model system to study the mechanisms that orchestrate diverse cellular processes. Oogenesis starts from asymmetric stem cell division, proper differentiation and the production of fully patterned oocytes equipped with all the maternal information required for embryogenesis. Spati...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9020274
更新日期：2020-01-22 00:00:00
abstract：:Actin remodeling is frequently regulated by antagonistic activities driving protrusion and contraction downstream of Rac and Rho small GTPases, respectively. WAVE regulatory complex (WRC), which primarily operates downstream of Rac, plays pivotal roles in neuronal morphogenesis. Recently, two independent studies descr...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9061355
更新日期：2020-05-29 00:00:00
abstract：:Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9010079
更新日期：2019-12-28 00:00:00
