The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

Inhibition of fungal plant pathogens by synergistic action of chito-oligosaccharides and commercially available fungicides

Chitosan is a linear heteropolymer consisting of β 1,4-linked N-acetyl-D-glucosamine (GlcNAc) and D-glucosamine (GlcN). We have compared the antifungal activity of chitosan with DPn (average degree of polymerization) 206 and FA (fraction of acetylation) 0.15 and of enzymatically produced chito-oligosaccharides (CHOS) of different DPn alone and in combination with commercially available synthetic fungicides, against Botrytis cinerea, the causative agent of gray mold in numerous fruit and vegetable crops. CHOS with DPn in the range of 15-40 had the greatest anti-fungal activity. The combination of CHOS and low dosages of synthetic fungicides showed synergistic effects on antifungal activity in both in vitro and in vivo assays. Our study shows that CHOS enhance the activity of commercially available fungicides. Thus, addition of CHOS, available as a nontoxic byproduct of the shellfish industry, may reduce the amounts of fungicides that are needed to control plant diseases

The isolation of chitinase from Streptomyces thermocarboxydus and its application in the preparation of chitin oligomers

[[abstract]]Microbial chitinase has received great attention due to its medical, biological, and agricultural applications. In this study, over 50 bacterial strains were isolated from Taiwanese soils using medium containing squid pen powder (SPP) as the sole source of carbon/nitrogen. Based on chitinolytic activity, Streptomyces thermocar-boxydus TKU045 was selected for further study. Optimized culture conditions revealed that S. thermocarboxydus TKU045 could produce the highest chitinase activity (52.985 U/mL) when cultured in a medium containing 1% (w/v) SPP at 45 °C for 36h. Characterized TKU045 chitinase showed novel properties with a smallest molecular weight (12.8 kDa by sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis) and more acidic optimal pH (pH 4) than those of other Streptomyces chitinases. A combination of high-performanceliquid chromatography and matrix-assisted laser desorption ionization time of flight mass spectrometer data revealed that chitin oligomers (COS) obtained from the hydrolysis of colloidal chitin by TKU045 chitinase comprise oligomers with multiple degrees of polymerization (DP) varying from 1 to 7. The COS with low DP exhibited enhanced 2,2-diphenyl-1-picrylhydrazyl radical scavenging capability and promoted the growth of Lactoba-cillus lactis. Taken together, the COS obtained by hydrolyzing colloidal chitin with TKU045 chitinase could have the potential to be used in medicine or nutraceuticals due to its active anti-oxidant and prebiotic contents.[[sponsorship]]科技部[[notice]]補正完