University of Macau

About: University of Macau is a education organization based out in Macao, Macau, China. It is known for research contribution in the topics: Population & Control theory. The organization has 6636 authors who have published 18324 publications receiving 327384 citations. The organization is also known as: UM & UMAC.

cAMP Response Element-Binding Protein (CREB): A Possible Signaling Molecule Link in the Pathophysiology of Schizophrenia

Abstract: Dopamine is a brain neurotransmitter involved in the pathology of schizophrenia The dopamine hypothesis states that, in schizophrenia, dopaminergic signal transduction is hyperactive The cAMP-response element binding protein (CREB) is an intracellular protein that regulates the expression of genes that are important in dopaminergic neurons Dopamine affects the phosphorylation of CREB via G protein-coupled receptors Neurotrophins, such as brain derived growth factor (BDNF), are critical regulators during neurodevelopment and synaptic plasticity The CREB is one of the major regulators of neurotrophin responses since phosphorylated CREB binds to a specific sequence in the promoter of BDNF and regulates its transcription Moreover, susceptibility genes associated with schizophrenia also target and stimulate the activity of CREB Abnormalities of CREB expression is observed in the brain of individuals suffering from schizophrenia, and two variants (-933T to C and -413G to A) were found only in schizophrenic patients The CREB was also involved in the therapy of animal models of schizophrenia Collectively, these findings suggest a link between CREB and the pathophysiology of schizophrenia This review provides an overview of CREB structure, expression, and biological functions in the brain and its interaction with dopamine signaling, neurotrophins, and susceptibility genes for schizophrenia Animal models in which CREB function is modulated, by either overexpression of the protein or knocked down through gene deletion/mutation, implicating CREB in schizophrenia and antipsychotic drugs efficacy are also discussed Targeting research and drug development on CREB could potentially accelerate the development of novel medications against schizophrenia

Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics

Abstract: Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.