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Today, 12 Ιουλίου 2016, 4:18:46 μμ
Medication-Induced Nephrotoxicity in Older Patients
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Objective: To summarize current evidence about mechanisms, clinical features, diagnostic issues, and strategies for prevention of medication-induced nephrotoxicity among older people. </p><p> Methods: A Pubmed search was performed, and studies concerning age-related changes in kidney structure and function predisposing to nephrotoxicity, pathophysiological mechanisms, kidney drug metabolism enzymes, clinical epidemiology of medication-induced kidney damage, biomarkers for early identification of nephrotoxicity and strategies for prevention of medication-induced nephrotoxicity among older people were selected. Finally, 245 papers were included in the review. </p><p> Results: Medications may induce nephrotoxicity through several pathophysiological mechanisms. People aged 75 or more are especially exposed to potential nephrotoxic medications or combinations of medications in the context of complex polypharmacy regimens. Estimated glomerular filtration rate (eGFR) may be useful to identify medication-induced alterations in kidney function, but creatinine-based methods have important limitation in older patients. Several innovative biomarkers have been proposed to identify AKI but these methodologies are not standardized and older people have not been evaluated systematically. Factors related to patient, medication, and interactions should be taken into account for effective prevention. </p><p> Conclusions: Medication-induced nephrotoxicity is a relevant problem in older populations. Nevertheless, several areas of uncertainty remain to be explored, including the impact of nephrotoxicity on functional outcomes relevant to older patients, the reliability of currently recommended methods for diagnosing and staging AKI, the use of innovative biomarkers in such a heterogeneous population, the effectiveness of preventing strategies and treatments and their impact on functional outcomes. </p><p>
Metformin - The Drug for the Treatment of Autoimmune Diseases; A New Use of a Known Anti-Diabetic Drug
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Autoimmune diseases are characterized by the production of autoantibodies directed against specific organs of own organism. Additional common traits of autoimmune diseases are chronic inflammation due to generation of inflammatory mediators, and disorders of redox processes. The pathogenesis of autoimmune diseases is still unknown. Treatment is based only on relieving the symptoms and improving the quality of patients lives. Metformin, which is used in treatment of type 2 diabetes, has properties which are desirable for autoimmune disease therapy, including anti-inflammatory and antioxidant effects, and the ability to regenerate the endothelium.
Oxidative Stress in Polycystic Ovary Syndrome
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Backgrouund: Polycystic ovary syndrome is a multifaceted disorder with a pathogenetic pathway that is not fully understood yet. Apart from hormonal derangements, insulin signaling defects and adipose tissue dysfunction, oxidative stress, defined as an imbalance derived from excessive formation of oxidants in the presence of limited antioxidants defenses, has been actively implicated in the etiology of the syndrome. Methods: This review focuses on understanding the putative role of oxidative stress in the pathophysiology of PCOS and analyzing its interconnection with the rest etiologic parameters and its contribution to the reproductive and metabolic manifestations of the syndrome. Results: Although underlying mechanisms have not been fully elucidated yet, it becomes evident that oxidative stress holds a respectable share in the pathogenesis of PCOS. In fact, PCOS can be considered as a purely oxidative state, where the body antioxidants cannot outweigh the excessive production of free radicals. Conclusion: Oxidative stress, in conjunction with the rest etiologic mechanisms of PCOS and the cardinal contribution of environmental factors, leads to an adverse redox status that stigmatizes the natural process of the syndrome.
Taste and Hypertension in Humans: Targeting Cardiovascular Disease
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The association between salty taste and NaCl intake with hypertension is well-established, although it is far from completely understood. Other taste types such as sweet, umami or bitter have also been related to alterations in blood pressure. Here, we review the mutual relationship between taste and hypertension to identify potential avenues to better control blood pressure. This review focuses on published data involving humans, with the exception of a section on molecular mechanisms. There is compelling evidence to suggest that changes in salty taste sensitivity can be used to predict the onset of hypertension. This goes hand in hand with the medical concept of sodium sensitivity, which also increases with age, particularly in hypertensive patients. The association of hypertension with the loss of taste acuity less definitive with some data/conclusions masked by the use of anti-hypertensive drugs. In fact, this group of therapeutic agents can reduce food taste perception resulting in mild to severe hypogeusia and dysgeusia. In the elderly, antihypertensive drugs may lead to a loss of appetite, thus, selecting treatments with low or no impact on taste perception should be advised. Pharmacological approaches to mitigate cardiovascular disease (CVD) could well take a different spin in the future following the discovery of taste receptors (TAS1R and TAS2R) in the cardiovascular system. Finally, long-term dietary strategies to minimize the risk of development of hypertension and CVD are discussed identifying several nutrients and public health policies with relevant potential.
Metabolic Basis of Polycystic Ovarian Syndrome; Indications for Biochemical Screening
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Background: Polycystic ovary syndrome (PCOS) is a heterogeneous condition with wide range of phenotype the cause of this disorder is unknown, however, increased ovarian androgen production including increased theca cell responsiveness to gonadotropin stimulation, increased pituitary secretion of luteinizing hormone, and hyperinsulinemia have been suggested. Some known risk factors are ethnicity and environmental factors including lifestyle and bodyweight. </p><p> Method: Relevant English language studies from January 1995 to September 2015 were identified, reviewed, synthesized and discussed extensively. </p><p> Result: various forms of PCOS, and the underlying mechanisms; and highlights biochemical, morphological and metabolic hallmarks of PCOS, including trends and emerging phenotypes; and presents a simplified synthesis that integrates current understanding of biochemical and metabolic endocrinology of PCOS are summarized. As no generally accepted criteria exist for its diagnosis, some existing diagnostic criteria that cut across different geographical regions are also highlighted. </p><p> Conclusion: Indeed, emerging evidence points that the severity of menstrual problems could serve as a predictor of the like-hood of insulin resistance in women of reproductive age, suggesting the need for routine metabolic screening and early intervention in PCOS. </p><p>
Activation of the dsRNA-Activated Protein Kinase PKR in Mitochondrial Dysfunction and Inflammatory Stress in Metabolic Syndrome
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Background: The double stranded RNA (dsRNA)-activated protein kinase PKR is a well-established protein kinase that is activated by dsRNA during viral infection, and it inhibits global protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation factor 2 (eIF2 ). Recent studies have greatly broadened the recognized physiological activities of PKR by demonstrating its fundamental role in inflammatory signaling, particularly in chronic, low-grade inflammation induced by metabolic disorders, known as metaflammation. Metaflammation is initiated by the activation of the NOD-like receptor (NLR), leucine-rich repeat, pyrin domaincontaining 3 (NLRP3) gene by mitochondrial reactive oxygen species (ROS). A protein complex defined as the metaflammasome is assembled in the course of metaflammation. This complex integrates nutritional signaling with cellular stress, inflammatory components, and insulin action and is essential in maintaining metabolic homeostasis. PKR is a key constituent of the metaflammasome and interacts directly with several inflammatory kinases, such as inhibitor B (I B) kinase (IKK) and c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS1), and component of the translational machinery such as eIF2 . Conclusion: This review highlights recent findings in PKR-mediated metaflammation and its association with the onset of metabolic syndrome in both human and animal models, with a focus on the molecular and biochemical pathways that underlie the progression of obesity, insulin resistance, and type-2 diabetes.
Polypharmacological Drugs in the Treatment of Epilepsy: The Comprehensive Review of Marketed and New Emerging Molecules
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Epilepsy is a complex neurological disorder which has plagued the human population through the ages and continues to affect about 50 million people worldwide. A better understanding of the pathogenesis of epilepsy unmasks various molecular targets for the treatment of epilepsy. The currently used antiepileptic drugs (AEDs) predominately target voltage-gated ion channels (Na<sup>+</sup>, Ca<sup>2+</sup> and K<sup>+</sup>), GABAA receptor, glutamate receptor, synaptic vesicle 2A (SV2A) protein and carbonic anhydrase (CA). One group of AEDs acts on a single target while another group acts via multiple targets to control seizure episodes. AEDs which act via multiple mechanisms or polypharmacological mechanisms of action have appeared as broad spectrum anticonvulsant agent and therefore, they provide a better choice to clinicians to manage drug-resistant epilepsies and various other epileptic syndromes. For example, polypharmacological AEDs such as PB, VPA, OXC, FBM etc. are vital for managing epilepsy successfully, since decades. In literature there is no review available which exclusively highlights the polypharmacological mechanisms of action of existing AEDs as well as new emerging molecules. This review covers running marketed AEDs, clinical trial drugs as well as potent preclinical molecules which displayed anti-epileptic activity via multiple mechanisms of action and this appraisal will surely provide a base for discovering potent multi-targeted AEDs.
Barriers to Risk Stratification Accuracy in Ischemic Heart Disease in Women: The Role of Non-Obstructive Coronary Artery Disease
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Background: A substantial part of literature has been centered on sex differences in the clinical aspects of ischemic heart disease (IHD). Many reports have documented differences in the presentation and risk profile between women and men. Such differences drive sex-related inequalities in the referral and treatment of IHD. Yet data are insufficient to clarify the reasons for such disparities. The objective of this review is to analyze the main gender differences regarding symptoms, diagnosis, and risk stratification of coronary heart disease in order to identify “gaps” in existing literature that need to be addressed in future research efforts. Methods: We searched English-language studies on MEDLINE and the Cochrane Database of Systematic Reviews from the database start dates to January 2016. Evidence synthesis was based on cohort studies, registry data, and clinical trial data. Results: Women do not often participate in clinical studies. In a number of articles, authors have questioned how the "white male” came to be the prototype of the human research subject. Consequently although many reports continue to describe differential treatment based on patients’ sex, the extent to which such inequalities are due to true sex differences in pathophysiology or whether they reflects inaccuracy in risk stratification is unclear. Conclusion: Today, even the best database is incapable in and of itself of supplying answers to the question of whether women are being treated less compared with men by the medical community.
Narcolepsy in Adolescents: A Review and Three Case Reports
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Background: Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic and/or hypnopompic hallucinations, and sleep paralysis. Due to symptom overlap and comorbidity between narcolepsy and other psychiatric disorders, narcolepsy in children and adolescents can be easily misdiagnosed. Diagnostic delay is common. </p><p> Method: We review the clinical presentations, epidemiology, etiology, diagnostic criteria, and treatment of this disabling disorder. We also present three examples of cases initially diagnosed as either a medical or psychiatric disorder, leading to a delay in management ranging from seven months to seven years. </p><p> Discussion: These cases highlight the importance for psychiatrists and other mental health professionals who work with adolescents to become familiar with this uncommon disorder to shorten time to treatment of this patient population. </p><p>
Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia
Today, 12 Ιουλίου 2016, 4:18:47 μμ
There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. </p><p> In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. </p><p> Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. </p><p> In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. </p><p> Key Points: </p><p> • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. </p><p> • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. </p><p>
Anosmin 1 Interacts with the Prokineticin Receptor 2 In Vitro Indicating a Molecular Link Between Both Proteins in the Pathogenesis of Kallmann Syndrome
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Sexual maturation and olfactory bulb defects found in prokineticin 2 (Pk2) and prokineticin receptor 2 (Pkr2) mutant mice resembling the phenotypic characteristics of Kallmann syndrome (KS), gave rise to the question of whether these genes would have a role in KS pathogenesis. Later, mutations in both genes were identified in patients suffering from KS. The gene responsible for the Xlinked form of KS, ANOS1, encodes the ECM protein anosmin 1. Among other functions, anosmin 1 can regulate the activity of FGFR1, encoded by one of the genes involved in the autosomal transmission of KS. Therefore, it has been proposed that anosmin 1 could interact with PKR2 to modulate its activity. We present the first evidence supporting this hypothesis and report the interaction of full-length anosmin 1 with three extracellular domains of PKR2. A truncated anosmin 1 protein comprising the first three domains of the protein interacts with the second extracellular loop of PKR2, involved in PK2 binding. Finally, last three FnIII repeats of anosmin 1 also interacted with the PKR2 domains that interacted with full-length anosmin 1. Our data represent a molecular link between two of the genes involved in KS pathogenesis.
The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Long-term potentiation (LTP) and long-term depression (LTD) are two distinct forms of synaptic plasticity that have been extensively characterized at the Schaffer collateral-CA1 (SCCA1) synapse and the mossy fiber (MF)-CA3 synapse within the hippocampus, and are postulated to be the molecular underpinning for several cognitive functions. Deficits in LTP and LTD have been implicated in the pathophysiology of several neurological and psychiatric disorders. Therefore, there has been a large effort focused on developing an understanding of the mechanisms underlying these forms of plasticity and novel therapeutic strategies that improve or rescue these plasticity deficits. Among many other targets, the metabotropic glutamate (mGlu) receptors show promise as novel therapeutic candidates for the treatment of these disorders. Among the eight distinct mGlu receptor subtypes (mGlu<sub>1-8</sub>), the mGlu<sub>1,2,3,5,7</sub> subtypes are expressed throughout the hippocampus and have been shown to play important roles in the regulation of synaptic plasticity in this brain area. However, development of therapeutic agents that target these mGlu receptors has been hampered by a lack of subtype-selective compounds. Recently, discovery of allosteric modulators of mGlu receptors has provided novel ligands that are highly selective for individual mGlu receptor subtypes. The mGlu receptors modulate the multiple forms of synaptic plasticity at both SC-CA1 and MF synapses and allosteric modulators of mGlu receptors have emerged as potential therapeutic agents that may rescue plasticity deficits and improve cognitive function in patients suffering from multiple neurological and psychiatric disorders.
Oxidative Stress Genes, Antioxidants and Coronary Artery Disease in Type 2 Diabetes Mellitus
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The worldwide increasing prevalence of obesity and sedentary lifestyle is the main cause of the rising incidence of T2DM. Due to chronic macrovascular and microvascular complications, T2DM represent a huge socioeconomic burden in the world. Oxidative stress is a key pathogenic mechanism implicated in diabetic coronary artery disease (CAD). Polymorphisms of oxidative stress genes are known to influence oxidative stress levels and are therefore thought to impact CAD pathogenesis. Identifying higher risk groups would be rational, since it would allow better sample selection and thus better results in antioxidant trials. In this review, we summarize the evidence of oxidative stress gene polymorphisms related to the pathogenesis of CAD. Moreover, we provide a review of antioxidants tested in subjects with CAD.
Oncotarget Strategies For Herpes Simplex Virus-1
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The high level of manipulability of viral genome has set up HSV-1 to be an ideal viral vector for oncolytic virotherapy. In the past two decades, several oncolytic HSV-1 viruses have been successfully developed and assessed in animal studies. Accumulated evidences show that oncolytic HSV- 1 can efficiently infect many tumor cells and augment anti-tumor effect by induction of systemic innate and adaptive immune responses. Inspiring results have been accomplished in several phase I clinical trials for glioma, head and neck squeous cells carcinoma and Melanoma using oncolytic HSV- 1 viruses. More recently, oncovey, one of oncolytic HSV-1 viruses has been approved by FDA for the comprehensive evolution of its anti-tumor effects in phase III clinical trials. These promising studies encourage more efforts to be devoted to craft the new generation of oncolytic HSV-1. Herein, we will review and summarize the basic strategies to construct oncolytic HSV-1 viruses and their applications in cancer therapy.
Correlation between Systemic Lupus Erythematosus Activity and Plasma Levels of Monomeric Prolactin and Macroprolactin
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The correlation of prolactin (PRL) levels with SLE activity is a controversial issue, which could be explained by the presence of macroprolactin (MPRL), a high molecular weight form of PRL with a lower in vivo biological activity. </p><p> Objectives: We aimed to evaluate the prevalence of hyperprolactinemia, PRL and MPRL levels in SLE patients, and to correlate these levels with disease activity as measured by the SLE Disease Activity Index (SLEDAI). </p><p> Material and Methods: We conducted a case-control, cross-sectional study with 73 SLE patients (L group), sixty-two of which were evaluated before and after treatment, and correlated the results with serum PRL and MPRL levels. These results were compared to those of 29 healthy women with ovulatory cycles (C group) and 34 women in the third trimester of pregnancy (G group). </p><p> Results: Mean PRL levels were: 8,8 ng/ml on C group; 12,0 ng/ml on L group (p = 0.02) and 158,5 ng/ml on G group. Hyperprolactinemia was present in 19.4% of SLE patients, but was not found on C group. The MPRL form was predominant among 20.5% of SLE patients, in none of the C group and in only 5.8% of pregnant women. There was a strong correlation between the PRL levels and SLE activity, regardless of the hormone’s molecular form. SLE treatment was able to reduce levels of all forms of PRL. The predominance of MPRL, however, did not change after treatment. </p><p> Conclusions: Despite its lower biological activity, MPRL levels correlated with LES activity as much as free prolactin. </p><p>
Effects of Yokukansan, a Japanese Kampo Medicine for Symptoms Associated Autism Spectrum Disorder
Today, 12 Ιουλίου 2016, 4:18:47 μμ
A neuropsychiatric syndrome, Autism spectrum disorder (ASD) is qualified via impairments in qualitative communication, social interaction, and stereotyped or restricted, repetitive patterns of behavior, interests, or activities. While all ASDs are considered to have qualitative deficits in social relatedness to others, many people with ASDs have other symptoms, including irritability (which includes aggression, self-injurious behavior, and severe tantrums). In order to decrease these behaviors, it is often helpful to make use of behavioral therapy. In addition, due to the intensity and severity of irritability, adjunctive medications are sometimes needed. Although many of the adjunctive medications have been tested and demonstrated to be useful in treating ASD, no clear standardized treatment has emerged. While the adjunctive medications have shown efficacy, the associated side effects have proven to be a barrier to their accepted use. A traditional Japanese medicine, Yokukansan (YKS), is composed of seven kinds of dried herbs and is widely clinically prescribed for treating psychiatric disorders by acting mainly on the glutamatergic and serotonergic nervous systems. YKS may be safe and useful in treating dementia patients’ behavioral and psychological symptoms according to indications from recent studies. We introduce in this review, the ameliorative effects of YKS on Asperger's disorder in open-label studies and on ASDs including pervasive developmental disorder not otherwise specified (PDD-NOS). This review will suggest that YKS is well tolerated and effective for the treatment for subjects with ASD who have severe hyperactivity/noncompliance and irritability/agitation. Additionally, the serotonergic, glutamatergic, anti-inflammatory and neurogenesis effects are explored which are thought to be involved in the mechanisms underlying the efficacy of YKS.
AMPK As A Target in Rare Diseases
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The AMP-activated protein kinase (AMPK) has emerged as an important sensor of signals that control cellular energy balance in all eukaryotes. AMPK is also involved in fatty acid oxidation, glucose transport, antioxidant defense, mitochondrial biogenesis and the modulation of inflammatory processes. The numerous roles of AMPK in cell physiological and pathological states justified the notable increase in the number of publications in previous years, with almost 1500 scientific articles relative to this kinase in 2014. Due to its role in maintaining energy balance, a dysfunction in AMPK signalling pathway may result in perturbations at the systemic level that contribute to the development of many disease conditions. Among them, more than 7000 poorly-known rare diseases are particularly of social and scientific interest because they are usually chronically debilitating or even lifethreatening and lack effective and safe treatment. Several authors have demonstrated AMPK alterations and the beneficial effect of treatments with drugs regulating AMPK activity in some of these low prevalence pathologies. Among these rare diseases in which AMPK can play an important pathological role are mitochondrial disorders, muscular dystrophies, cardiovascular diseases, neurodegenerative pathologies, or even some types of cancer for the importance of AMPK as a suppressor of cell proliferation. This review focuses on current knowledge about the pathophysiological roles of AMPK and future approaches as therapeutic targeting in rare diseases.
Tapentadol PR for Pain Syndromes in Real Life Patients with Hematological Malignancy
Today, 12 Ιουλίου 2016, 4:18:47 μμ
Background: More than 50% of oncohematological patients suffer from pain syndrome, mostly originating from the bone, which often include nociceptive and neuropathic complaints. Tapentadol, a recently available treatment option for cancer pain, exerts a dual analgesic mechanisms (opioid and noradrenergic), allowing for a high clinical efficacy as well as for a reduction in adverse events compared to traditional opioids. </p><p> Aim: To explore the safety and efficacy of tapentadol as a suitable agent for the pain management in the setting of oncohematology. </p><p> Methods: Our observational study included 36 patients with basal pain intensity (NRS) ranging from 5 to 10. Tapentadol prolonged release (PR) was given at the initial dose of 50 mg BID and careful titrated according to the achieved pain control. Results. Tapentadol PR was given at the dosages ranging from 200 and 260 mg/day after a careful titration, allowed for a clinically (-7 points NRS) remarkable reduction of pain intensity without any significant side effects. </p><p> Conclusion: In oncohematological patients on pain, tapentadol PR was effective and well tolerated, so representing a suitable treatment option in this difficult setting. </p><p>
Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Today, 12 Ιουλίου 2016, 4:18:47 μμ
A-kinase anchoring proteins (AKAPs) control the localization of cAMP-dependent protein kinase A (PKA) by tethering PKA to distinct cellular compartments. Through additional direct proteinprotein interactions with PKA substrates and other signaling molecules they form multi-protein complexes. Thereby, AKAPs regulate the access of PKA to its substrates in a temporal and spatial manner as well as the local crosstalk of cAMP/PKA with other signaling pathways. Due to the increasing information on their molecular functioning and three-dimensional structures, and their emerging roles in the development of diseases, AKAPs move into the focus as potential drug targets. Targeting AKAP dependent protein-protein interactions for interference with local signal processing inside cells potentially allows for the development of therapeutics with high selectivity and fewer side effects.
Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases
Today, 12 Ιουλίου 2016, 4:18:47 μμ
The calcium binding protein S100B has attracted great attention as a biomarker for a variety of diseases. S100B is mainly expressed in glial cells and functions through intracellular and extracellular signaling pathways. The biological roles of S100B have been closely associated with its concentrations and its physiological states. The released S100B can bind to the receptor of advanced glycation end products and induce the initiation of multiple cell signaling transductions. The regulation of S100B bioactivities has been suggested through phosphoinositide 3 kinase/Akt, p53, mitogen-activated protein kinases, transcriptional factors including nuclear factor-kappaB, and cyclic adenosine monophosphate. The levels of S100B in the blood may function to predict the progress or the prognosis of many kinds of diseases, such as cerebrovascular diseases, neurodegenerative diseases, motor neuron diseases, traumatic brain injury, schizophrenia, depression, diabetes mellitus, myocardial infarction, cancer, and infectious diseases. Given that the activity of S100B has been implicated in the pathological process of these diseases, S100B should not be simply regarded as a biomarker, it may also function as therapeutic target for these diseases. Further elucidation of the roles of S100B may formulate innovative therapeutic strategies for multiple diseases.
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