An Alternate View of Neuroprotection with Peptides in Alzheimer’s Disease

Neuroprotection plays a crucial role in everyday life, maintaining a clean environment in the central nervous system to allow for normal functioning. In Alzheimer’s disease and other neurodegenerative disorders, neuroprotection may have two roles. Under standard circumstances, the immune system protects the CNS, but sometimes it can exacerbate the pathophysiology of some diseases through neuroinflammation leading to further degeneration. Alzheimer’s disease is fast getting out of control, with no new approvals in therapeutics since 2003, and of those approved, all target symptomatic treatment. Initiated by a microglial response to Aβ plaques, therapeutic development should focus on the amyloid cascade as a neuroprotective measure for Alzheimer’s disease. This chapter will examine the status of the types of therapeutics in clinical trials for Alzheimer’s disease, offering insights into peptides as an area of opportunity for neuroprotection and detailing considerations for the use of peptides in Alzheimer’s disease

MathBench: improvement of quantitative skills for life science undergraduates via online modules

Much has been reported on the need to improve quantitative skills (QS) in science. Finding ways to respond to this has been the subject of many recent studies. The MathBench-Australia project responded to the need for blended learning resources that target undergraduate QS in biology. The MathBench biology modules were originally developed at the University of Maryland (UMD), USA. The MathBench-Australia project contextualized and adapted the modules for the benefit of science undergraduate students in Australian universities, in collaboration with colleagues of the MathBench-USA team. The choice of biology as the science discipline of focus is aligned with the Chief Scientist’s (2012) report on the persistent popularity of biology courses not only among first year but among continuing undergraduate science students in Australia. Brown (2009), in his report to the Group of Eight universities, noted that good mathematics preparation was an advantage for Australian science students, even for those studying “biology, a discipline not traditionally associated with strong mathematics preparation”. Thus, it was anticipated that uptake of learning resources such as MathBench could have a significant long-term impact on the improvement of QS among science students in Australia. Indeed, this was observed in our OLT-funded MathBench-Australia project grant, among our partner universities, which will be presented and discussed in this presentation. Office of the Chief Scientist. (2012). Health of Australian Science. Brown, G. (2009). Review of education in mathematics, data science and quantitative disciplines: Report to the Group of Eight Universities

Exploring the effects of omega-3 and omega-6 fatty acids on allergy using a HEK-blue cell line.

BACKGROUND: Allergic reactions can result in life-threatening situations resulting in high economic costs and morbidity. Therefore, more effective reagents are needed for allergy treatment. A causal relationship has been suggested to exist between the intake of omega-3/6 fatty acids, such as docosahexanoic acid (DHA), eicosapentanoic acid (EPA), docosapentanoic acid (DPA) and arachidonic acid (AA), and atopic individuals suffering from allergies. In allergic cascades, the hallmark cytokine IL-4 bind to IL-4 receptor (IL-4R) and IL-13 binds to IL-13 receptor (IL-13R), this activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE antibody production by B cells. The overall aim of this study was to characterize omega-3/6 fatty acids and their effects on STAT6 signaling pathway that results in IgE production in allergic individuals. METHODS: The fatty acids were tested in vitro with a HEK-Blue IL-4/IL-13 reporter cell line model, transfected with a reporter gene that produces an enzyme, secreted embryonic alkaline phosphatase (SEAP). SEAP acts as a substitute to IgE when cells are stimulated with bioactive cytokines IL-4 and/or IL-13. RESULTS: We have successfully used DHA, EPA and DPA in our studies that demonstrated a decrease in SEAP secretion, as opposed to an increase in SEAP secretion with AA treatment. A statistical Student\u27s t-test revealed the significance of the results, confirming our initial hypothesis. CONCLUSION: We have successfully identified and characterised DHA, EPA, DPA and AA in our allergy model. While AA was a potent stimulator, DHA, EPA and DPA were potential inhibitors of IL-4R/IL-13R signalling, which regulates the STAT6 induced pathway in allergic cascades. Such findings are significant in the future design of dietary therapeutics for the treatment of allergies

Fishy business : effect of omega-3 fatty acids on zinc transporters and free zinc availability in human neuronal cells

Omega-3 (ω-3) fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA). The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer\u27s disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s) for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration

A new approach to the investigation of allergenic respirable particles using a modified Anderson Impactor

Pollen allergens have been shown to occur in fine particles much smaller than pollen grains. As such allergenic particles have a high probability of entering the lower human airways, it is important to further investigate their origin and their biological and immunological properties. Accordingly, we have modified the particle collection surface of an Andersen Impactor using adhesive coated microscope slides to enable identification by high resolution microscopic analysis and immunodetection of allergenic particulates.<br /

Zinc and DHA have opposing effects on the expression levels of histones H3 and H4 in human neuronal cells

Zn and DHA have putative neuroprotective effects and these two essential nutrients are known to interact biochemically. We aimed to identify novel protein candidates that are differentially expressed in human neuronal cell line M17 in response to Zn and DHA that would explain the molecular basis of this interaction. Two-dimensional gel electrophoresis and MS were applied to identify major protein expression changes in the protein lysates of human Ml7 neuronal cells that had been grown in the presence and absence of Zn and DHA. Proteomic findings were further investigated using Western immunoblot and real-time PCR analyses. Four protein spots, which had significant differential expression, were identified and selected for in-gel trypsin digestion followed by matrix-assisted laser desorption ionisation MS analysis. The resultant peptide mass fingerprint for each spot allowed their respective identities to be deduced. Two human histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the presence of Zn (physiological condition). These proteomic findings were further supported by Western immunoblot and real-time PCR analyses using H3- and H4-specific monoclonal antibodies and oligonucleotide primers, respectively. We propose that dietary Zn and DHA cause a global effect on gene expression, which is mediated by histones. Such novel information provides possible clues to the molecular basis of neuroprotection by Zn and DHA that may contribute to the future treatment, prevention and management of neurodegenerative diseases such as Alzheimer\u27s disease.<br /

Immunological comparison of native and recombinant hen\u27s egg yolk allergen, chicken serum albumin (Gal d 5), produced in Kluveromyces lactis

Chicken serum albumin (CSA) is a hen\u27s egg yolk allergen causing IgE-mediated allergy. The objective of this study was to produce a recombinant version of CSA and compare its IgE reactivity to natural CSA (nCSA). CSA was cloned and expressed as a soluble fraction in the yeast Kluyveromyces lactis (K. lactis) protein expression system. The gene encoding CSA was amplified with a C-terminal hemagglutinin epitope tag by polymerase chain reaction (PCR) and cloned into the pKLAC2 expression vector prior to transforming into K. lactis. Recombinant CSA (rCSA) was purified by immunoprecipitation. Twenty-one patients allergic to hen\u27s egg white were examined for sensitisation against nCSA. 38% of patients were found to be sensitised to CSA based on Western immunoassay. Immunoglobulin E (IgE) binding capacity of rCSA and nCSA was analysed by ELISA using sera from patients sensitised to CSA. Levels of IgE-binding were similar for both the recombinant and the natural CSA, indicating the existence of similar epitopes. rCSA produced in this study is a potential candidate to be used in component-resolved diagnosis (CRD) of egg yolk allergy. The usefulness of rCSA in CRD of egg yolk allergy warrants further characterisation using sera from patients with allergy to hen\u27s egg yolk in future studies