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Current Drug Targets

Ana C N Oliveira, Joana Fernandes, Anabela Goncalves, Andreia C Gomes, Real Oliveira
The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers have been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties...
July 3, 2018: Current Drug Targets
Tiantian Wang, Hongchen He, Shaxin Liu, Chengsen Jia, Ziyan Fan, Can Zhong, Chengqi He
Autophagy is a process the primary role of which is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Osteoporosis associated with aging is characterized by consistent changes in bone metabolism with suppression of bone formation as well as increased bone resorption. In advanced age, not only bone mass but also bone strength decrease in both sexes, resulting in an increased incidence of fractures. Clinical and animal experiments reveal that age-related bone loss is associated with many factors such as accumulation of autophagy, increased levels of reactive oxygen species, sex hormone deficiency, and high levels of endogenous glucocorticoids...
June 26, 2018: Current Drug Targets
Himadri Singh, Vijayalakhsmi Venkatesan
Obesity is a prominent risk factor for type 2 diabetes. Management of type 2 diabetes requires weight management in addition to glycemic parameters. For obese type 2 diabetes patients, metformin, Sodium-glucose co-transporter-2 inhibitors or Glucagon-Like Peptide-1 Receptor Agonists should be prescribed as the first priority for controlling both hyperglycemia and body weight or fat distribution. The Combination of these drugs with sulfonylureas, thiazolidinediones, and insulin may also be required in chronic cases...
June 20, 2018: Current Drug Targets
Kunal Kalra, Srijaya Thekkeparambil Chandrabose, Thamil Selvee Ramasamy, Noor Hayaty Binti Abu Kasim
Diabetes mellitus is one of the leading cause for death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans onsets and progresses diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced pluripotent stem cells (hiPSC), holds potential for treating diabetes owning to their self-renewal capacity and ability to differentiate into β-cells...
June 4, 2018: Current Drug Targets
Jiang Haiying, Takeshi Sasaki, Enze Jin, Masafumi Kuzuya, Xianwu Cheng
Abdominal aortic aneurysm (AAA), a common disease among elderly individuals, involves the progressive dilatation of the abdominal aorta as a consequence of degeneration. The mechanisms of AAA formation, development and rupture are largely unknown. Surgical repair is the only available method of treatment since the lack of knowledge regarding the pathogenesis of AAA has hindered the development of suitable medical treatments, particularly the development of drugs. In this review, we describe the inflammatory cells and proteases that may be involved in the formation and development of AAA...
May 30, 2018: Current Drug Targets
Manisha Pandey, Hira Choudhury, Cheah Xiao Yi, Chen Wei Mun, Goh Khang Ping, Guee Xin Rou, Bhalqish Jeet Kaur A/P Ambar Jeet Singh, Angel Ng Ann Jhee, Lee Kai Chin, Prashant Kesharwani, Bapi Gorain, Zahid Hussain
Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major researches are ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions...
May 22, 2018: Current Drug Targets
Rashidi Mohamed Pakri Mohamad, Jaya Kumar, Shihab Udin Ahmad, Isa Naina Mohamed
In the past two decades, the search for novel pharmacotherapies to treat alcohol addiction been a global endeavour. This has resulted in several drugs that have been approved and successfully marketed for public use while some are still in the testing phase. These pharmacological agents, though effective for the treatment of alcoholism, are not without shortcomings; such as abuse potential, serious mental and physical adverse effects, interaction with alcohol and also poor metabolism and excretion. As more is being understood about the neurobiology of alcohol addiction as well as the unique pharmacological action of these drugs, new agents are evaluated for potential benefits when used as a adjunct in combination therapy...
May 22, 2018: Current Drug Targets
Claudia Arenaccio, Chiara Chiozzini, Flavia Ferrantelli, Patrizia Leone, Eleonora Olivetta, Maurizio Federico
BACKGROUND: Eukaryotic cells release vesicles of different sizes under both physiological and pathological conditions. On the basis of the respective biogenesis, extracellular vesicles are classified as apoptotic bodies, microvesicles, and exosomes. Among these, exosomes are considered tools for innovative therapeutic interventions, especially when engineered with effector molecules. The delivery functions of exosomes are favored by a number of typical features. These include their small size (i...
May 20, 2018: Current Drug Targets
Jie Feng, Yandong Li, Yu Nie
Heart failure represents a challenging clinical and public health problem and is associated with significant morbidity and mortality. Mechanistically, loss of cardiomyocytes leads to decompensated ventricular remodeling, which eventually progressed to cardiac failure. Regenerative medicine aimed to supplement functional cardiomyocytes is supposedly a promising approach for the effective treatment of heart failure. Over the past decades, investigations on heart regeneration have revealed the regulating networks of cardiomyocyte proliferation...
May 17, 2018: Current Drug Targets
Nian Fu, XueFeng Yang, Linxi Chen
Nucleophagy is a selective autophagy, which selectively remove damaged or non-essential nuclear material from a cell by the autophagy pathway. Additionally, nucleophagy is crucial for promoting cell longevity and ensure body proper function. Increasing evidences have shown that nucleophagy may play a major role in such human diseases as degenerative disorders, tumorigenesis, malnutrition and metabolic disorders, parakeratosis and psoriasis. Studies indicated that nucleophagy can improve degenerative disorders by delaying premature cell senescence, prevent malnutrition and metabolic disorder via maintaining nuclear structure and releasing nutrients for energy production, and alleviate parakeratosis and psoriasis...
May 17, 2018: Current Drug Targets
Lifeng Wang, J Chen, C Ning, D Lei, Jun Ren
Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem and a common cause of chronic liver diseases. However, the underlying mechanisms leading to the development and progression of NAFLD remain elusive. Accumulating evidence has depicted an essential role for endoplasmic reticulum (ER) stress in the development of steatosis and later progression into nonalcoholic steatohepatitis and hepatocarcinoma. With the accumulation of unfolded and misfolded proteins in the ER lumen, ER stress is provoked to turn on the unfolded protein response (UPR)...
May 16, 2018: Current Drug Targets
Rajiv Janardhanan
The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities...
May 14, 2018: Current Drug Targets
Anna Woodbury, Myles R McCrary, Shan P Yu
This chapter explores therapeutic targets and the anti-inflammatory nature of some naturally-occurring compounds and the current or potential use of these compounds in the treatment of chronic inflammatory pain states. We will review the mechanisms of chronic inflammatory pain, the molecular targets of selected natural compounds in inhibiting inflammatory pain, and the traditional and current approaches to treating pain using these compounds. Previous research on experimental as well as clinical pain will be summarized from in vitro to animal and human models...
May 14, 2018: Current Drug Targets
Dianaly T Au, Allison L Arai, William E Fondrie, Selen C Muratoglu, Dudley K Strickland
Aortic aneurysms represent a significant clinical problem as they largely go undetected until a rupture occurs. Currently, an understanding of mechanisms leading to aneurysm formation is limited. Numerous studies clearly indicate that vascular smooth muscle cells play a major role in the development and response of the vasculature to hemodynamic changes and defects in these responses can lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth muscle cell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate and regulate signaling pathways...
May 11, 2018: Current Drug Targets
Ling Shiao Ling, Hatta Sidi, Raja Adam Raja Lope, Srijit Das, Azlin Baharudin
Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively...
May 11, 2018: Current Drug Targets
Danuh Kim, Hyun Joo Kim, Seunghyun Ahn
Despite widespread clinical use of anesthetics, the exact mechanisms of anesthetic action are unclear. In terms of physiological action, a broad mechanism of general anesthesia including perturbations of neurotransmission has been suggested. The mechanism of anesthetic action at the molecular level is less clear, however. Specifically, how anesthetics affect neurons and glial cells and which proteins those anesthetics interact with remains to be explored. Several recent studies have investigated the molecular interactions between proteins and anesthetics...
May 1, 2018: Current Drug Targets
Abdul Mannan Baig
Despite advances in drug discovery and modifications in the chemotherapeutic regimens, human infections caused by free-living amoebae (FLA) have high mortality rates (~95%). The FLA that cause fatal human cerebral infections include Naegleria fowleri, Balamuthia mandrillaris and Acanthamoeba spp. Novel drug-target discovery remains the only viable option to tackle these central nervous system (CNS) infection in order to lower the mortality rates caused by the FLA. Of these FLA, N. fowleri causes primary amoebic meningoencephalitis (PAM), while the A...
April 25, 2018: Current Drug Targets
Irshad Ahmad, Nighat Nawaz, Fatemeh Karimi Dermani, Alisa Khodadadi Kohlan, Massoud Saidijam, Simon G Patching
Antimicrobial resistance is a global challenge, for which the mechanisms of resistance are varied and complicated. Bacterial multidrug efflux proteins are a major mechanism of antimicrobial resistance and therefore targets for drug development. Gram-negative bacteria are intrinsically more resistant to many antibiotics and biocides due to their cell structure and the activity of multidrug efflux proteins. These transporters actively extrude antibiotics and other xenobiotics from the cytoplasm or surrounding membranes of cells to the external environment...
April 25, 2018: Current Drug Targets
Hugo A Garro, Carlos R Pungitore
BACKGROUND: The discovery of new chemotherapeutic agents still remains a continuous goal to achieve. DNA polymerases and topoisomerases act in nucleic acids metabolism modulating different processes like replication, mitosis, damage repair, DNA topology and transcription. It has been widely documented that Polymerases serve as molecular targets for antiviral and antitumoral chemotherapy. Furthermore, telomerase is a ribonucleoprotein with exacerbated activity in most of tumor cell lines, becoming as an emergent target in Cancer treatment...
April 25, 2018: Current Drug Targets
Asli F Ceylan, Sidney Y Ren
Diabetes is an important cause of morbidity and mortality in worldwide. Management of blood glucose is critical for diabetic patients since diabetes carries risk for many diseases and disorders. Although there are several antidiabetic agents in the markets for a long time, some of the agents have dose-limiting side effects, such as hypoglycemia and weight gain which limits their ability to reduce cardiovascular complications. Sodium glucose co-transporter 2 (SGLT2) inhibitors are new class of antidiabetic agents which exerts their effects insulin-independent mechanism therefore they do not cause hypoglycemia in the diabetic patients...
April 19, 2018: Current Drug Targets
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