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Expert Opinion on Therapeutic Targets

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https://read.qxmd.com/read/30871383/th17-cells-a-promising-therapeutic-target-for-parkinson-s-disease
#1
Iryna Prots, Beate Winner
Parkinson's disease (PD) is the most common neurodegenerative movement disorder caused by the progressive loss of neurons in the midbrain and other brain regions. Only symptomatic treatment is currently available. Mounting evidence suggests that T cells are a key contributor to PD pathogenesis and neurodegeneration by a mechanism that requires further elucidation. Areas covered: We discuss the evidence of imbalanced activation of effector T cell populations in PD and summarize the data of Th17 involvement and Th17-regulated mechanisms in PD pathology...
March 14, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30856027/tumor-necrosis-factor-receptor-2-tnfr2-an-overview-of-an-emerging-drug-target
#2
Juliane Medler, Harald Wajant
Tumor necrosis factor (TNF) receptor 2 (TNFR2) is one of two receptors of the cytokines, TNF and lymphotoxin-κ. TNFR1 is a strong inducer of proinflammatory activities. TNFR2 has proinflammatory effects too, but it also elicits strong anti-inflammatory activities and has protective effects on oligodendrocytes, cardiomyocytes and keratinocytes. The protective and anti-inflammatory effects of TNFR2 may explain why TNF inhibitors failed to be effective in diseases such as heart failure or multiple sclerosis, where TNF has been strongly implicated as a driving force...
March 11, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30810053/the-emergence-of-ephexin5-as-a-therapeutic-target-in-alzheimer-s-disease
#3
Emily K Cook, Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
No abstract text is available yet for this article.
February 27, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30802415/current-strategies-toward-safer-mu-opioid-receptor-drugs-for-pain-management
#4
Aliza T Ehrlich, Brigitte L Kieffer, Emmanuel Darcq
Pain relief remains a major public health challenge. The most efficient available painkillers are opioids targeting the mu opioid receptor (MOR). MORs are expressed in the areas of the brain [including pain and respiratory centers] that are important for processing reward and aversion. Thus, MOR activation efficiently alleviates severe pain, but the concomitant reward and respiratory depressant effects pose a threat; patients taking opioids potentially develop opioid addiction and high risk for overdose. Areas covered: Ongoing efforts to generate safer opioid analgesics are reviewed here...
February 25, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30801205/the-use-of-lp533401-as-a-therapeutic-option-for-renal-osteodystrophy-affects-renal-calcium-handling-vitamin-d-metabolism-and-bone-health-in-uremic-rats
#5
Dariusz Pawlak, Tomasz Domaniewski, Beata Znorko, Krystyna Pawlak
BACKGROUND: Klotho is a key regulator of phosphate and Ca2+ - transport in the kidney. Recently, we showed that treatment with LP533401 improved bone health in rats with chronic kidney disease (CKD) via the normalization of serum phosphate resulting from the reduced renal expression of phosphate co-transporters, including Klotho. METHODS: We evaluated the effect of LP533401 therapy on Klotho-expression dependent Ca2+ - transporters, renal calcium handling and the potential consequences for the bone of uremic rats...
February 25, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30801204/targeting-metabotropic-glutamate-receptors-in-the-treatment-of-epilepsy-rationale-and-current-status
#6
Roberta Celli, Ines Santolini, Gilles van Luijtelaar, Richard T Ngomba, Valeria Bruno, Ferdinando Nicoletti
Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors. These receptors mediate fast excitatory synaptic transmission in the central nervous system (CNS) and their blockade may cause severe adverse effects such as sedation, cognitive impairment and psychotomimetic effects...
February 25, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30764678/agmatine-as-a-potential-therapeutic-intervention-in-bipolar-depression-the-preclinical-landscape
#7
Devon Watts, Bianca Pfaffenseller, Bianca Wollenhaupt-Aguiar, Luiza Paul Géa, Taiane de Azevedo Cardoso, Flavio Kapczinski
Present antidepressant treatments are only helpful in a quarter of patients with bipolar depression, and new strategies are warranted. Increasing evidence suggests that accelerated polyamine metabolism is associated with the pathophysiology of depression. Polyamines regulate stress responses, inflammation, and neuronal signaling in the central and enteric nervous system. Agmatine is a promising target of altered polyamine metabolism considering its unique ability to regulate intracellular polyamine content and neuroprotective effects...
February 15, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30759030/biology-and-targeting-of-the-jumonji-domain-histone-demethylase-family-in-childhood-neoplasia-a-preclinical-overview
#8
Tyler S McCann, Lays M Sobral, Chelsea Self, Joseph Hsieh, Marybeth Sechler, Paul Jedlicka
Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia. Areas covered: The Jumonji-domain histone demethylase (JHDM) family exemplifies many of the above traits. This review summarizes the current state of knowledge of the functions and pharmacologic targeting of JHDMs in cancer and other neoplastic processes, with an emphasis on diseases affecting the pediatric population...
February 13, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30732494/the-nkg2d-axis-an-emerging-target-in-cancer-immunotherapy
#9
Mariya Lazarova, Alexander Steinle
The immunoreceptor NKG2D belongs to the best-characterized activating receptors of cytotoxic lymphocytes. NKG2D binds to a variety of cell surface glycoproteins distantly related to MHC class I molecules, termed NKG2D ligands (NKG2DL). NKG2DL are inducibly expressed upon cellular stress, viral infection or malignant transformation thus marking 'stressed' or 'harmful' cells for clearance through NKG2D+ lymphocytes. However, certain viruses and many tumors employ various strategies to escape from NKG2D-mediated immunosurveillance...
February 8, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30724632/e2f1-as-a-molecular-drug-target-in-ovarian-cancer
#10
Rossella Farra, Barbara Dapas, Mario Grassi, Fabio Benedetti, Gabriele Grassi
No abstract text is available yet for this article.
February 6, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30701991/grk2-and-grk5-as-therapeutic-targets-and-their-role-in-maladaptive-and-pathological-cardiac-hypertrophy
#11
Melissa Lieu, Walter J Koch
One in every four deaths in the United States is attributed to cardiovascular disease, hence the development and employment of novel and effective therapeutics are necessary to improve the quality of life and survival of affected patient. Pathological hypertrophy is a maladaptive response by the heart to relieve wall stress that could result from cardiovascular disease. Maladaptive hypertrophy can lead to further disease progression and complications such as heart failure; hence, efforts to target hypertrophy to prevent and treat further morbidity and mortality are necessary...
January 31, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30700216/functional-genetic-evaluation-of-dna-house-cleaning-enzymes-in-the-malaria-parasite-dutpase-and-ap4ah-are-essential-in-plasmodium-berghei-but-itpase-and-ndh-are-dispensable
#12
Hirdesh Kumar, Jessica Kehrer, Mirko Singer, Miriam Reinig, Jorge M Santos, Gunnar Mair, Friedrich Frischknecht
BACKGROUND: Cellular metabolism generates reactive oxygen species. The oxidation and deamination of the deoxynucleoside triphosphate (dNTP) pool results in the formation of non-canonical, toxic dNTPs that can cause mutations, genome instability and cell death. House-cleaning or sanitation enzymes that break down and detoxify non-canonical nucleotides play major protective roles in nucleotide metabolism and constitute key drug targets for cancer and various pathogens. We hypothesized that owing to their protective roles in nucleotide metabolism, these house-cleaning enzymes are key drug targets in the malaria parasite...
January 31, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30691318/the-p2x7-receptor-a-new-therapeutic-target-in-alzheimer-s-disease
#13
Peter Illes, Patrizia Rubini, Lumei Huang, Yong Tang
Alzheimer's disease (AD) is a neurodegenerative illness with genetic risk as an etiological factor in a subset of cases. In AD with autosomal dominant inheritance, the extracellular β-amyloid (Aβ) aggregates and intracellular neurofibrillary tangles which consist of hyperphosphorylated tau, appear to be involved in the neuronal damage; however, other forms of AD may have a polygenetic causality. Microglial cells orchestrate pathophysiological events responsible for neuronal damage in AD. They surround Aβ aggregates and the stimulation of microglial P2X7 receptors (P2X7Rs) by high local concentrations of ATP which originates from damaged CNS cells, results in degeneration of nearby neurons...
January 28, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30661441/neuronal-and-behavioral-plasticity-the-role-of-serotonin-and-bdnf-systems-tandem
#14
Nina K Popova, Vladimir S Naumenko
Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as principal players in different kinds of plasticity. The 5-HT-BDNF interaction in early ontogeny and in adult brain is an intriguing problem. Area covered: This paper concentrates on the interaction between 5-HT and BDNF systems and its implication in different plasticity levels, from neurons to behavior. This review describes: 1. different 5-HT functioning in the embryonic (as neurotrophin) and adult brain (as a neurotransmitter) 2. BDNF as a modulator of 5-HT system and vice versa 3 the prolonged positive effect of BDNF on genetically- and epigenetically-defined CNS disorders; 4...
January 21, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30650992/the-map-kinase-interacting-kinases-mnks-as-targets-in-oncology
#15
Jianling Xie, James E Merrett, Kirk B Jensen, Christopher G Proud
The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are switched on by the oncogenic MAPK (ERK) signalling pathway. They phosphorylate eukaryotic initiation factor (eIF) 4E, a protein which recruits ribosomes to mRNAs and thereby mediates their translation. Importantly, overexpression of eIF4E can transform cells, and its function is controlled by a second oncogenic pathway, mechanistic target of rapamycin complex 1. Areas covered: We have evaluated the literature related to the role of the MNKs in human cancers, including their control by oncogenic signalling pathways; their expression and regulation in cancer cells and preclinical cancer models; their roles on the proliferation, survival and migration/invasion of cancer cells...
January 16, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30678498/involvement-of-long-non-coding-rna-hulc-highly-up-regulated-in-liver-cancer-in-pathogenesis-and-implications-for-therapeutic-intervention
#16
Christiane Klec, Tony Gutschner, Katrin Panzitt, Martin Pichler
HULC (highly upregulated in liver cancer) is a long non-coding RNA (lncRNA) which is, as its name suggests, highly upregulated in hepatocellular carcinoma and in several other cancers. Increased HULC expression levels are strongly associated with clinicopathologic features such as tumor stages and overall survival and is a driver of tumor proliferation, migration, and invasion. Areas covered: This review addresses the discovery of HULC and discusses the consequences of HULC deregulation in cancer, the underlying molecular mechanisms and the potential of HULC as a biomarker and therapeutic target...
January 15, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30616404/pro-and-anti-tumorigenic-functions-of-the-senescence-associated-secretory-phenotype
#17
Lena Lau, Gregory David
Cellular senescence is a stable form of cell-cycle exit. Though they no longer divide, senescent cells remain metabolically active and secrete a plethora of proteins collectively termed the senescence-associated secretory phenotype (SASP). Although senescence-associated cell-cycle exit likely evolved as an anti-tumor mechanism, the SASP contains both anti- and pro-tumorigenic potential. Areas covered: In this review, we briefly discuss the discovery of senescent cells and its relationship to cancer and aging...
January 8, 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30580640/targeting-mitochondrial-quality-control-for-treating-sarcopenia-lessons-from-physical-exercise
#18
Anna Picca, Riccardo Calvani, Christiaan Leeuwenburgh, Hélio José Coelho-Junior, Roberto Bernabei, Francesco Landi, Emanuele Marzetti
Mitochondrial dysfunction is a hallmark of aging and hence is a candidate target for intervention. Sarcopenia of aging is a prevalent condition and is associated with numerous negative health outcomes. Alterations in mitochondrial homeostasis have been reported in sarcopenic muscle. Area covered: We discuss the evidence that points to mitochondrial dysfunction having a causative role in sarcopenia and the mechanisms involved in the accumulation of damaged mitochondria in the aged muscle. We also discuss the effects of physical exercise on mitochondrial quality control and muscle health in advanced age...
February 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30556755/targeting-hedgehog-pathway-in-pediatric-acute-myeloid-leukemia-challenges-and-opportunities
#19
Andrea Pession, Annalisa Lonetti, Salvatore Bertuccio, Franco Locatelli, Riccardo Masetti
No abstract text is available yet for this article.
February 2019: Expert Opinion on Therapeutic Targets
https://read.qxmd.com/read/30556751/cd73-as-a-potential-opportunity-for-cancer-immunotherapy
#20
Ghasem Ghalamfarsa, Mohammad Hossein Kazemi, Sahar Raoofi Mohseni, Ali Masjedi, Mohammad Hojjat-Farsangi, Gholamreza Azizi, Mehdi Yousefi, Farhad Jadidi-Niaragh
Cancer cells apply various mechanisms to induce and enhance immune escape. The complex network of immune-response modulating factors in the tumor microenvironment is a reason for the difficulties encountered when attempting to treat many cancers. Adenosine is a potent immune-modulating factor that can be generated through the degradation of ATP by cooperative action of NTPDase1 (CD39) and ecto-5'-nucleotidase (CD73) molecules. Overexpression of CD73 on tumor and immune cells leads to the presence of a high concentration of this factor in the tumor region...
February 2019: Expert Opinion on Therapeutic Targets
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