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Expert Opinion on Therapeutic Targets

Joshua Bloom, Shan Sun, Yousef Al-Abed
Macrophage migration inhibitory factor (MIF) has emerged as a promising drug target in diseases including sepsis, rheumatoid arthritis, and cancer. MIF has multiple properties that favor development of specific, targeted therapies: it is expressed broadly among human cells, has noted roles in diverse inflammatory and oncological processes, and has intrinsic enzymatic activity amenable to high-throughput screening. Despite these advantages, anti-MIF therapy remains well behind other cytokine-targeted therapeutics, with no small molecules in the pipeline for clinical development and anti-MIF antibodies only recently beginning clinical trials...
October 20, 2016: Expert Opinion on Therapeutic Targets
Shuai Jiang, Yang Yang, Tian Li, Zhiqiang Ma, Wei Hu, Chao Deng, Chongxi Fan, Jianjun Lv, Yang Sun, Wei Yi
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a basic leucine zipper (bZIP) transcription factor of the cap'n'collar (CNC) family that is present in various organs. The cardiovascular system (CVS) is susceptible to a spectrum of diseases that are strongly associated with increased risks of mortality and morbidity, and studies have demonstrated that Nrf2 has a pivotal role in protection against cardiovascular diseases (CVDs). Areas covered: Nrf2 is a basic protective molecule that guards against CVD by attenuating oxidative stress, mitochondrial dysfunction, and inflammation...
October 19, 2016: Expert Opinion on Therapeutic Targets
Mohammed Eslam, Jacob George
Type-III interferons (IFN-λ), the most recently discovered family of IFNs, shares common features with other family members, but also has many distinctive activities. IFN-λ uniquely has a different receptor complex, and a more focused pattern of tissue expression and signaling effects, from other classes of IFNs. Multiple genome-wide association studies (GWAS) and subsequent validation reports suggest a pivotal role for polymorphisms near the IFNL3 gene in hepatitis C clearance and control, as also for several other epithelial cell tropic viruses...
October 11, 2016: Expert Opinion on Therapeutic Targets
Michael Schweizer, Stephen Plymate
No abstract text is available yet for this article.
August 5, 2016: Expert Opinion on Therapeutic Targets
Ramkumar Menon, John Papaconstantinou
INTRODUCTION: Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. AREAS COVERED: Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition...
July 26, 2016: Expert Opinion on Therapeutic Targets
Sankar Jagadeeshan, Ganesh Venkatraman, Suresh K Rayala
No abstract text is available yet for this article.
November 2016: Expert Opinion on Therapeutic Targets
Kenji Hashimoto
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants since this drug causes rapid-onset and sustained antidepressant effects in treatment resistant patients with depression. There are unanswered questions about how ketamine induces its rapid and sustained antidepressant actions. This key article suggests that (2R,6R)-HNK (hydroxynorketamine), a major metabolite of (R)-ketamine, shows antidepressant effects in rodent models of depression, indicating that the metabolism of (R)-ketamine to (2R,6R)-HNK is pivotal in its antidepressant action...
November 2016: Expert Opinion on Therapeutic Targets
Kenji Hashimoto
No abstract text is available yet for this article.
October 2016: Expert Opinion on Therapeutic Targets
Marianna Colamaio, Nadia Tosti, Francesca Puca, Alessia Mari, Rosaria Gattordo, Yalçın Kuzay, Antonella Federico, Anna Pepe, Daniela Sarnataro, Elvira Ragozzino, Maddalena Raia, Hidenari Hirata, Marica Gemei, Koshi Mimori, Luigi Del Vecchio, Sabrina Battista, Alfredo Fusco
OBJECTIVE: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer...
October 2016: Expert Opinion on Therapeutic Targets
Kasey L Jackson, Robert D Dayton, Ronald L Klein
No abstract text is available yet for this article.
October 2016: Expert Opinion on Therapeutic Targets
Juan M Castellano, Manuel Tena-Sempere
INTRODUCTION: The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. AREAS COVERED: This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting...
October 2016: Expert Opinion on Therapeutic Targets
Neil T Hoa, Lisheng Ge, Filippo Martini, Vincent Chau, Amrita Ahluwalia, Carol A Kruse, Martin R Jadus
OBJECTIVE: Temozolomide (TMZ) improves Glioblastoma Multiforme (GBM) patient survival. The invasive behavior of the glioma cells is the cause of GBM relapse. The glioma BK ion channel (gBK) may provide glioma cells with a mechanism to invade surrounding tissue. gBK contains epitopes that cytolytic T lymphocytes (CTLs) can recognize and kill glioma cells. Fascin-1 is an actin crosslinking molecule that supports microvilli; these membrane protrusions provide a physical defense against CTLs...
October 2016: Expert Opinion on Therapeutic Targets
Sugunadevi Sakkiah, Hui Wen Ng, Weida Tong, Huixiao Hong
INTRODUCTION: Androgen receptor (AR) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. It plays a vital role in male sexual development and regulates gene expression in various tissues, including prostate. Androgens are compounds that exert their biological effects via interaction with AR. Binding of androgens to AR initiates conformational changes in AR that affect binding of co-regulator proteins and DNA. AR agonists and antagonists are widely used in a variety of clinical applications (i...
October 2016: Expert Opinion on Therapeutic Targets
Sami H Tuffaha, Prateush Singh, Joshua D Budihardjo, Kenneth R Means, James P Higgins, Jaimie T Shores, Roberto Salvatori, Ahmet Höke, W P Andrew Lee, Gerald Brandacher
INTRODUCTION: Peripheral nerve injuries often result in debilitating motor and sensory deficits. There are currently no therapeutic agents that are clinically available to enhance the regenerative process. Following surgical repair, axons often must regenerate long distances to reach and reinnervate distal targets. Progressive atrophy of denervated muscle and Schwann cells (SCs) prior to reinnervation contributes to poor outcomes. Growth hormone (GH)-based therapies have the potential to accelerate axonal regeneration while at the same time limiting atrophy of muscle and the distal regenerative pathway prior to reinnervation...
October 2016: Expert Opinion on Therapeutic Targets
Francesca Calabrese, Marco A Riva, Raffaella Molteni
INTRODUCTION: In recent years, the concept of 'synaptopathy' has been extended from neurodegenerative and neurological disorders to psychiatric diseases. According to this nascent line of research, disruption in synaptic structure and function acts as the main determinant of mental illness. Therefore, molecular systems and processes crucial for synaptic activity may represent promising therapeutic targets. AREAS COVERED: We review data on synaptic structural alterations in depression and schizophrenia and on specific molecular systems and/or mechanisms important for the maintenance of proper synaptic function...
October 2016: Expert Opinion on Therapeutic Targets
Bieke Van der Veken, Guido Ry De Meyer, Wim Martinet
INTRODUCTION: Atherosclerosis is a lipid-driven inflammatory process with a tremendously high mortality due to acute cardiac events. There is an emerging need for new therapies to stabilize atherosclerotic lesions. Growing evidence suggests that intraplaque (IP) neovascularisation and IP hemorrhages are important contributors to plaque instability. AREAS COVERED: Neovascularization is a complex process that involves different growth factors and inflammatory mediators of which their individual significance in atherosclerosis remains poorly understood...
October 2016: Expert Opinion on Therapeutic Targets
Zhentao Zhang, Manling Xie, Keqiang Ye
INTRODUCTION: Asparagine endopeptidase (AEP) is a pH-dependent endolysosomal cysteine protease that cleaves its substrates after asparagine residues. Our most recent study identifies that it possesses the delta-secretase activity, and that it is implicated in numerous neurological diseases such as Alzheimer's disease (AD) and stroke. Accumulating evidence supports that the inhibition of AEP exhibits beneficial effects for treating these devastating diseases. AREAS COVERED: Based on recent evidence, it is clear that AEP cleaves its substrate, such as amyloid precursor protein (APP), tau and SET, and plays a critical role in neuronal cell death in various neurodegenerative diseases and stroke...
October 2016: Expert Opinion on Therapeutic Targets
Paul Pévet
INTRODUCTION: Disorders of rhythmicity can cause a variety of pathologies and are known to impair processes involved in metabolism, as well as in cardiovascular disease and cancer. Developing strategies to treat or prevent such diseases is a new challenge for medicine. Rhythms depend on a complex multi-oscillatory circadian network which, in mammals, is hierarchically organized with the suprachiasmatic nuclei (SCN) as master clock. The SCN, thus form an ideal structure for target discovery in circadian pathologies...
October 2016: Expert Opinion on Therapeutic Targets
Robert Ramer, Burkhard Hinz
INTRODUCTION: Molecular structures of the endocannabinoid system have gained interest as potential pharmacotherapeutical targets for systemic cancer treatment. AREAS COVERED: The present review covers the contribution of the endocannabinoid system to cancer progression. Particular focus will be set on the accumulating preclinical data concerning antimetastatic, anti-invasive and anti-angiogenic mechanisms induced by cannabinoids. EXPERT OPINION: The main goal of targeting endocannabinoid structures for systemic anticancer treatment is the comparatively good safety profile of cannabinoid compounds...
October 2016: Expert Opinion on Therapeutic Targets
Elham Al Kubaisy, Kholoud Arafat, Olivier De Wever, Ahmed H Hassan, Samir Attoub
OBJECTIVE: Breast cancer is the most common cancer seen in women worldwide and breast cancer patients are at high risk of recurrence in the form of metastatic disease. Identification of genes associated with invasion and metastasis is crucial in order to develop novel anti-metastasis targeted therapy. It has been demonstrated that the DEAD-BOX helicase DP103 was implicated in breast cancer invasion and metastasis. SMARCAD1 is also a DEAD/H box-containing helicase, suggested to play a role in genetic instability...
September 2016: Expert Opinion on Therapeutic Targets
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