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Expert Opinion on Therapeutic Targets

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https://www.readbyqxmd.com/read/29671352/huntington-s-disease-novel-therapeutic-perspectives-hanging-in-the-balance
#1
Ana Saavedra, Gerardo García-Díaz Barriga, Esther Pérez-Navarro, Jordi Alberch
Huntington's disease (HD), an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin gene, has long been characterized by the presence of motor symptoms due to the loss of striatal projection neurons. Cognitive dysfunction and neuropsychiatric symptoms are also present and they occur in the absence of cell death in most mouse models, pointing to neuronal dysfunction and abnormal synaptic plasticity as causative mechanisms. Areas covered: Here, we focus on those common mechanisms altered by the presence of mutant huntingtin affecting corticostriatal and hippocampal function as therapeutic targets that could prove beneficial to ameliorate both cognitive and motor function in HD...
April 19, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29667529/emerging-therapeutic-targets-for-neurofibromatosis-type-1
#2
James A Walker, Meena Upadhyaya
Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited tumor predisposition syndrome with an incidence of one in 3000-4000 individuals with no currently effective therapies. The NF1 gene on chromosome 17 encodes neurofibromin, which functions as a negative regulator of RAS. NF1 is a chronic multi-system disorder affecting many different tissues. Due to cell-specific complexities of RAS signaling, therapeutic approaches for NF1 will likely have to focus on a particular tissue and manifestation of the disease...
April 18, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29658361/myd88-as-a-therapeutic-target-for-inflammatory-lung-diseases
#3
Franco Di Padova, Valerie F J Quesniaux, Bernhard Ryffel
Introduction Myeloid differentiation primary response protein 88 (MyD88) is a critical adaptor protein involved in Toll-like and IL-1 receptor family signaling controlling innate immune responses and inflammation. Genetic deletion of MyD88 function results in profound suppression of inflammation and reduced resistance of the host to pathogens indicating non-redundant roles of MyD88. The TIR domain is critical for MyD88 dimerization and signaling for TLR and IL-1R family receptor. Areas covered Emerging evidence suggests that chemical disruption of the TIR domain attenuates cell activation and inhibits in vivo MyD88-dependent inflammation...
April 16, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29637789/do-preclinical-studies-suggest-that-cd99-is-a-potential-therapeutic-target-in-acute-myeloid-leukemia-and-the-myelodysplastic-syndromes
#4
Montreh Tavakkoli, Stephen S Chung, Christopher Y Park
No abstract text is available yet for this article.
April 11, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29634426/potential-roles-of-tumor-derived-exosomes-in-angiogenesis
#5
Nils Ludwig, Theresa L Whiteside
Tumor-derived exosomes (TEX) and their role in tumor progression by accelerating angiogenesis are of great current interest. A better understanding of the mechanisms underlying TEX-blood vessels cross-talk may lead to improvements in current diagnosis, prognosis and treatment of cancer. Areas covered: For solid tumors, an adequate blood supply is of critical importance for their development, growth and metastasis. TEX, virus-size vesicles which circulate freely throughout body fluids and accumulate in the tumor microenvironment (TME), have been recognized as a new contributor to angiogenesis...
April 10, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29561217/immunological-mutational-signature-in-adenosquamous-cancer-of-pancreas-an-exploratory-study-of-potentially-therapeutic-targets
#6
Nicola Silvestris, Oronzo Brunetti, Rosamaria Pinto, Daniela Petriella, Antonella Argentiero, Livia Fucci, Stefania Tommasi, Katia Danza, Simona De Summa
OBJECTIVES: Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP...
March 27, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29542343/interplay-between-the-key-proteins-of-serotonin-system-in-ssri-antidepressants-efficacy
#7
Alexander V Kulikov, Raul R Gainetdinov, Evgeni Ponimaskin, Allan V Kalueff, Vladimir S Naumenko, Nina K Popova
Selective serotonin reuptake inhibitors (SSRIs) are the most effective and most used antidepressant drugs. Acting by inhibiting serotonin (5-HT) transporter, SSRIs display a typical 3-4-week delay in their therapeutic effects, with nearly 40% of depressed patients remaining treatment-resistant. Recent evidence suggests complex interplay between 5-HT receptors and key proteins of 5-HT metabolism in molecular mechanisms of such delay and resistance to SSRIs. Area covered: This paper concentrates on the interplay between 5-HT receptors in the delay of therapeutic effect of SSRIs, and the interaction between tryptophan hydroxylase 2 and 5-HT transporter in the SSRI resistance...
March 15, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29532697/foxp3-treg-as-a-therapeutic-target-for-promoting-anti-tumor-immunity
#8
Theresa L Whiteside
Regulatory T cells (Treg) characterized by expression of FOXP3 and strong immunosuppressive activity play a key role in regulating homeostasis in health and disease. Areas covered: Human Treg are highly diverse phenotypically and functionally. In the tumor microenvironment (TME), Treg are reprogrammed by the tumor, acquiring an activated phenotype and enhanced suppressor functions. No unique phenotypic markers for Treg accumulating in human tumors exist. Treg are heterogeneous and use numerous mechanisms to mediate suppression, which either silences anti-tumor immune surveillance or prevents tissue damage by activated T cells...
March 13, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29528755/emerging-therapeutic-targets-for-the-treatment-of-malignant-rhabdoid-tumors
#9
Karolina Nemes, Michael C Frühwald
Malignant Rhabdoid Tumor (MRT) is a rare and highly aggressive malignancy primarily affecting infants and young children. The most common anatomic locations are the central nervous system (AT/RT), the kidneys (RTK) and other soft tissues (eMRT). The genetic origin of this disease is linked to mutations in SMARCB1, a gene encoding a core subunit of the SWI/SNF chromatin-remodeling complex. Areas covered: Conventional multimodal treatment may offer a significant survival benefit to certain patients. It remains to be determined, however, which patients will prove resistant to chemotherapy and need novel therapeutic approaches...
March 12, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29527929/notch-signaling-as-a-therapeutic-target-for-acute-lymphoblastic-leukemia
#10
Diana Bellavia, Rocco Palermo, Maria Pia Felli, Isabella Screpanti, Saula Checquolo
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease...
March 12, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29517391/evolution-of-gapdh-as-a-druggable-target-of-tumor-glycolysis
#11
Shanmugasundaram Ganapathy-Kanniappan
No abstract text is available yet for this article.
March 8, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29517390/targeted-therapy-to-annihilate-the-immune-evading-phenotype-in-cancer-evolution
#12
Ariel Fernández
No abstract text is available yet for this article.
March 8, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29504411/inducible-nitric-oxide-synthase-as-a-target-for-osteoarthritis-treatment
#13
Andreas Leonidou, Panagiotis Lepetsos, Michalis Mintzas, Eustathios Kenanidis, George Macheras, Maria Tzetis, Michael Potoupnis, Eleftherios Tsiridis
Inducible nitric oxide synthase (iNOS) is the enzyme responsible for the production of nitric oxide (NO), a major proinflammatory and destructive mediator in osteoarthritis (OA). Areas covered: This is a comprehensive review of the recent literature on the involvement of iNOS in osteoarthritis and its potential to be used as a target for OA treatment. Evidence from in vitro, in vivo and human studies was systematically collected using medical search engines. Preclinical studies have focused on the effect of direct and indirect iNOS inhibitors in both animal and human tissues...
March 5, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29468927/inducible-co-stimulator-icos-as-a-potential-therapeutic-target-for-anti-cancer-therapy
#14
Florent Amatore, Laurent Gorvel, Daniel Olive
The recent success of checkpoint-inhibitors in cancer treatment paved the way for the development of new strategies of agonist and antagonist agents against B7 superfamily members. Inducible Co-Stimulator (ICOS), a co-stimulatory receptor for T-cell enhancement, arouses interest. Areas covered: We performed an extensive literature search with PUBMED using the keywords 'ICOS' and 'cancer' to discuss its involvement in oncogenesis, its expression in different malignancies, and its targeting in relevant preclinical studies...
February 22, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29436254/therapeutic-targets-for-altering-mitochondrial-dysfunction-associated-with-diabetic-retinopathy
#15
Renu A Kowluru, Manish Mishra
Retinopathy remains as one of the most feared blinding complications of diabetes, and with the prevalence of this life-long disease escalating at an alarming rate, the incidence of retinopathy is also climbing. Although the cutting edge research has identified many molecular mechanisms associated with its development, the exact mechanism how diabetes damages the retina remains obscure, limiting therapeutic options for this devastating disease. Areas covered: This review focuses on the central role of mitochondrial dysfunction/damage in the pathogenesis of diabetic retinopathy, and how damaged mitochondria initiates a self-perpetuating vicious cycles of free radicals...
February 13, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29431050/tdp-43-post-translational-modifications-in-health-and-disease
#16
Emanuele Buratti
Nuclear factor TDP-43 is a ubiquitously expressed RNA binding protein that plays a key causative role in several neurodegenerative diseases, especially in the ALS/FTD spectrum. In addition, its aberrant aggregation and expression has been recently observed in other type of diseases, such as myopathies and Niemann-Pick C, a lysosomal storage disease. Areas Covered. This review aims to specifically cover the post-translational modifications (PTMs) that can affect TDP-43 function and cellular status both in health and disease...
February 10, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29431026/the-potential-of-aldehyde-dehydrogenase-2-as-a-therapeutic-target-in-cardiovascular-disease
#17
Thomas Münzel, Andreas Daiber
Mitochondrial aldehyde dehydrogenase (ALDH-2) plays a major role in the ethanol detoxification pathway by removing acetaldehyde. Therefore, ALDH-2 inhibitors such as disulfiram represent the first therapeutic targeting of ALDH-2 for alcoholism therapy. Areas covered: Recently, ALDH-2 was identified as an essential bioactivating enzyme of the anti-ischemic organic nitrate nitroglycerin, bringing ALDH-2 again into the focus of clinical interest. Mechanistic studies on the nitroglycerin bioactivation process revealed that during bioconversion of nitroglycerin and in the presence of reactive oxygen and nitrogen species the active site thiols of ALDH-2 are oxidized and the enzyme activity is lost...
February 10, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29421932/the-70-kda-heat-shock-protein-hsp70-as-a-therapeutic-target-for-stroke
#18
Jong Youl Kim, Yeonseung Han, Jong Eun Lee, Midori A Yenari
The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury...
February 8, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29417868/non-coding-rnas-as-therapeutic-targets-for-preventing-myocardial-ischemia-reperfusion-injury
#19
Sang-Bing Ong, Khairunnisa Katwadi, Xiu-Yi Kwek, Nur Izzah Ismail, Sang-Ging Ong, Kroekkiat Chinda, Derek J Hausenloy
New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI. Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI...
February 8, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29417861/the-potential-of-ar-v7-as-a-therapeutic-target
#20
Takuma Uo, Stephen R Plymate, Cynthia C Sprenger
The androgen receptor variant AR-V7 is gaining attention as a potential predictive marker for as well as one of the resistance mechanisms to the most current anti-androgen receptor (AR) therapies in castration-resistant prostate cancer (CRPC). Accordingly, development of next-generation drugs that directly or indirectly target AR-V7 signaling is urgently needed. Areas covered: We review proposed mechanisms of drug resistance in relation to AR-V7 status, the mechanisms of generation of AR-V7, and its transcriptome, cistrome, and interactome...
February 8, 2018: Expert Opinion on Therapeutic Targets
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