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Current Drug Targets

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Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial and life-threatening chronic infections in cystic fibrosis patients. This pathogen is well-known for its ability to attach to surfaces of indwelling medical devices to form biofilms, which consist of a regular array of extracellular polymers. Tenaciously bound to the surface of devices and inherently resilient to antibiotic treatment, P. aeruginosa poses a serious threat in clinical medicine and contributes to the persistence of chronic infections...
October 19, 2016: Current Drug Targets
Preeti Vyas, Divya Vohora
Recent findings have publicized phosphoinositide-3-kinases (PI3Ks) as novel therapeutic targets, which are also purported to be involved in the complex pathophysiology of inflammatory and various other diseases. They are recognized to participate in the inflammatory cellular responses by modulating the growth, development and proliferation of various immune cells and hence, affect the release of various cytokines and other inflammatory mediators involved in these manifestations. The review presents a brief synopsis of the PI3K/AKT/mTOR signalling pathway along with the current and future prospects of targeting PI3Ks for various diseases, like malignant, autoimmune, inflammatory, cardiovascular, neurological disorders etc...
October 13, 2016: Current Drug Targets
Silvia Tejada, William Setzer, Maria Daglia, Seyed Fazel Nabavi, Antoni Sureda, Nady Braidy, Olga Gortzi, Seyed Mohammad Nabavi
Neurodegenerative diseases are growing inexorably as the population ages, with enormous economic and social costs. The World Health Organization (WHO) has reported that by 2040, neurodegenerative diseases will overtake cancer to become the second leading cause of natural death, after cardiovascular diseases. Recent investigations suggest that the combination of genes and environmental toxins may contribute to the risk of developing neurodegenerative disorders. Thus, intervention strategies aimed at reducing exposure to risk factors such as life style, smoking, diet, vitamin deficiencies, chemical exposure and pollution are warranted...
October 5, 2016: Current Drug Targets
Syeda Mehpara Farhat, Touqeer Ahmed
Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds to α7 nicotinic acetylcholine receptors (nAChRs) with very high affinity. This discovery has led to extensive exploration of the possible outcomes of this binding, ranging from the subcellular signaling pathways to its effects on behavioral and cognitive functions...
October 5, 2016: Current Drug Targets
Silvia Tejada, Samuel Pinya, Maria Del Mar Bibiloni, Josep A Tur, Antoni Pons, Antoni Sureda
The Mediterranean diet includes olive oil as its primary source of fat. This diet is frequently associated to longevity and a lower incidence of chronic diseases thanks to its biological activities and health effects. Apart from oleic acid, olive oil contains many bioactive components including polyphenols that have been reported to exert antioxidant and anti-inflammatory activities. Polyphenols may for the most part be responsible for the protective effects against cardiovascular diseases associated with olive oil...
October 5, 2016: Current Drug Targets
Masamichi Yamashita
Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents lead to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms...
October 5, 2016: Current Drug Targets
Dalia Ibrahim Al-Dosary, Abdullah Saleh Alhomida, Mohammad Shamsul Ola
Diabetic retinopathy is one of the serious complications of diabetes and the leading cause of decreased vision and blindness worldwide. Neurodegeneration has been recognized as initiating factor in causing the retinal damage, which leads to micro-vascular damage in diabetic retinopathy. Diabetes-induced oxidative stress is believed to be the key factor that damages neurons in the diabetic retina. Various therapeutic approaches for effective attenuation of increased oxidative stress by antioxidants have emerged...
October 3, 2016: Current Drug Targets
Isabel Ferreira, Joana Liberal, João Martins, Ana Silva, Bruno M Neves, Maria Teresa Cruz
An intricate interplay between innate and adaptive immune cells is crucial for an effective immune response during disease, infection and vaccination. This interplay is manly performed by dendritic cells (DCs), which are professional antigen presenting cells (APCs) with unparalleled capacity to translate innate to adaptive immunity. They effectively recognize and uptake antigens, migrate to lymphoid tissues, and activate naïve T-cells. To enable rapid pathogen detection DCs utilize numerous germline encoded pattern recognition receptors (PRR) that recognize conserved pathogen associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs)...
September 21, 2016: Current Drug Targets
Xiangwei Liu, Aijun Sun
Coronary heart disease is the leading cause of mortality and morbidity, incurring a major burden of medical care. Even with increasing application of emergent recanalization (PCI and CABG) therapy, ischemia and ischemic reperfusion injury remain as the dominant pathological process that damages cardiomyocytes. Mitochondrial Aldehyde dehydrogenase-2 (ALDH2) is a multifunctional enzyme catalyzing the oxidation of aldehydes. Accumulating data have shown that ALDH2 can help restore mitochondria function by eliminating toxic aldehyde and participating in cellular signaling important for cell adaption and survival...
September 12, 2016: Current Drug Targets
Srijit Das, Seong Lin Teoh
The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression...
September 7, 2016: Current Drug Targets
Antonis S Manolis, Theodora A Manolis, Antonis A Manolis, Helen Melita
The thromboembolic risk of atrial fibrillation (AF) is significantly mitigated by oral anticoagulation (OAC) therapy, albeit at an increasing bleeding risk. The general principle is that the expected protective benefit of OAC must not exceed the potential harm conferred by possible bleeding. Over the recent years, the CHA2DS2-VASc score has been proven to be superior to other scores in identifying 'low risk' AF patients. However, even this latest score does not incorporate all possible risk factors causing a high thromboembolic risk, while the individual components of the CHA2DS2-VASc score do not seem to carry equal thromboembolic risk...
September 5, 2016: Current Drug Targets
Basak Topkoru, Emrah Egemen, Ihsan Solaroglu, John Zhang
Subarachnoid hemorrhage (SAH) following rupture of an intracranial is associated with high mortality and morbidity. The late deterioration of the patient's neurological status or late cognitive dysfunctions even after secure clipping or decent endovascular treatment which is defined as delayed ischemic neurological deficits recently has been attributed to vasospasm. Due to the failure of specific anti-vasospastic agents in clinical trials researchers focused to explore new pathological mechanisms to be responsible for the delayed deterioration of the patients suffering from SAH...
September 5, 2016: Current Drug Targets
Nirali N Shah
Despite great progress in the curative treatment of acute leukemia, outcomes for those with relapsed and/or chemotherapy-refractory disease remain poor. Current intensive cytotoxic therapies can be associated with significant morbidity and novel therapies are needed to improve outcomes. Immunotherapy based approaches provide an alternative mechanism of action in the treatment of acute leukemia. Due to cell surface antigen expression, leukemia in particular is amenable to targeted therapies, such as antibody-based therapy...
September 4, 2016: Current Drug Targets
Elena Fernandez Burguera, Rosa Meijide-Failde, Francisco J Blanco
Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues...
August 29, 2016: Current Drug Targets
Meera Ramanan, Mukesh Doble
Prostaglandins serve as the connecting link between inflammation and cancer. mPGES1, the downstream enzyme in the prostaglandin pathway is considered a better target than COX-2 against the progression of cancer due to the cardiovascular and other complications associated with the inhibition of the latter. Despite the discovery of several compounds that inhibit mPGES1 none could enter the market as drugs because of the problems concerning specificity and unacceptable pharmacokinetic properties. Expression of mPGES1 is inducible in conditions of inflammation and hypoxia and its expression is regulated by a number of transcriptional factors...
August 25, 2016: Current Drug Targets
Debabrata Chowdhury, Dinesh Kumar, Pranjal Sarma, Anjana Devi Tangutur, Manika Pal Bhadra
Prohibitin (PHB) is overtly conserved evolutionarily and ubiquitously expressed protein with pleiotropic functions in diverse cellular compartments. However, regulation and function of these proteins in different cells, tissues and in various diseases is different as evidenced by expression of these proteins which is found to be reduced in heart diseases, kidney diseases, lung disease, Crohn's disease and ulcerative colitis but this protein is highly expressed in diverse cancer diseases. The mechanism by which this protein acts at the molecular level in different subcellular localizations or in different cells or tissues in different conditions (diseases or normal) has remained poorly understood...
August 24, 2016: Current Drug Targets
Kamlesh Sharma
Protein farnesyltransferase (PFT) inhibitors have emerged as a potent target for the malaria treatment caused by the Plasmodium falciparum (Pf) parasite. In this review, various scaffolds as Pf-PFT inhibitors are reported. Seven inhibitor scaffolds based on ethylenediamine, peptidomimetic, benzophenone, benzamide, tetrahydroquinoline, naphthyridine and oxy-tetrahydroquinoline, have been developed. These inhibitors act against Pf-PFT target and have proved their therapeutic potential as antimalarial agents. This review is primarily meant for suggesting new drugs against malaria...
August 23, 2016: Current Drug Targets
Yuan Feng, Bo Li, Xue Yi Li, Zhen Biao Wu
Autophagy is an evolutionarily conserved degradation process in response to metabolic stress or changing environment. Autophagy induction involves formation of autophagosomes, which fuse with lysosomes and degrade encapsulated intracellular components, such as long-lived and misfolded proteins, as well as intracellular organelles. Autophagy has been implicated in a wide variety of physiological and pathological conditions. Emerging lines of evidence suggest a crucial role of autophagy in the regulation of immunity and inflammation...
August 19, 2016: Current Drug Targets
Wing Mann Ho, Cesar Reis, Onat Akyol, Gokce Yilmaz Akyol, Richard Applegate 2nd, Gary Stier, Robert Martin, John H Zhang
Hemorrhagic transformation (HT) is a common and natural complication after acute ischemic stroke. The only FDA-approved treatment so far for acute ischemic stroke is rapid reperfusion with recombinant tissue plasminogen activator (rtPA). Although it has been shown to exaggerate the risk and severity of HT and to be associated with increased morbidity and mortality. Understanding HT is essential to restore cerebral blood flow to ischemic brain by reperfusion therapy without causing this complication and additional brain injury...
August 18, 2016: Current Drug Targets
Sabena M Conley, Justine M Abais, Krishna M Boini, Pin-Lan Li
The intracellular multiprotein complex termed the inflammasome functions as a platform of pro-inflammatory cytokine production such as IL-1β and IL-18. Under certain conditions, however, the inflammasome produces non-canonical effects such as induction of cell death, pyroptosis and cell metabolism alterations. In mammalian cells, several types of inflammasomes were identified, but the most widely studied one is the inflammasome containing NOD-like receptor with pyrin domain 3 (NLRP3), which has recently been reported as a central pathogenic mechanism of chronic degenerative diseases...
August 17, 2016: Current Drug Targets
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