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Defining the molecular changes that underlie Alzheimer's disease (AD) is an important question in neuroscience. Here, we examined changes in protein SUMOylation, and proteins involved in mitochondrial dynamics, in an in vitro model of AD induced by application of amyloid-ß 1-42 (Aß1-42) to cultured neurons. We observed Aß1-42-induced decreases in global SUMOylation and in levels of the SUMO pathway enzymes SENP3, PIAS1/2, and SAE2. Aß exposure also decreased levels of the mitochondrial fission proteins Drp1 and Mff and increased activation of caspase-3. To examine whether loss of SENP3 is cytoprotective we knocked down SENP3, which partially prevented the Aß1-42-induced increase in caspase-3 activation. Together, these data support the hypothesis that altered SUMOylation may play a role in the mechanisms underlying AD.

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SUMOylation is a post-translational modification (PTM) whereby members of the Small Ubiquitin-like MOdifier (SUMO) family of proteins are conjugated to lysine residues in target proteins. SUMOylation has been implicated in a wide range of physiological and pathological processes, and much attention has been given to its role in neurodegenerative conditions. Due to its reported role in neuroprotection, pharmacological modulation of SUMOylation represents an attractive potential therapeutic strategy in a number of different brain disorders. However, very few compounds that target the SUMOylation pathway have been identified. Guanosine is an endogenous nucleoside with important neuromodulatory and neuroprotective effects. Experimental evidence has shown that guanosine can modulate different intracellular pathways, including PTMs. In the present study we examined whether guanosine alters global protein SUMOylation. Primary cortical neurons and astrocytes were treated with guanosine at 1, 10, 100, 300, or 500 µM at four time points, 1, 6, 24, or 48 h. We show that guanosine increases global SUMO2/3-ylation in neurons and astrocytes at 1 h at concentrations above 10 µM. The molecular mechanisms involved in this effect were evaluated in neurons. The guanosine-induced increase in global SUMO2/3-ylation was still observed in the presence of dipyridamole, which prevents guanosine internalization, demonstrating an extracellular guanosine-induced effect. Furthermore, the A1 adenosine receptor antagonist DPCPX abolished the guanosine-induced increase in SUMO2/3-ylation. The A2A adenosine receptor antagonist ZM241385 increased SUMOylation per se, but did not alter guanosine-induced SUMOylation, suggesting that guanosine may modulate SUMO2/3-ylation through an A1-A2A receptor interaction. Taken together, this is the first report to show guanosine as a SUMO2/3-ylation enhancer in astrocytes and neurons.

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Background: Although legume protein extracts are useful in food preparation and processing as foam stabilizers and as viscosity, palatability and nutrition enhancers, many legume proteins from South America have not been characterized extensively. One such legume is the ñuña bean (Phaseolus vulgaris L.), which is cooked using dry heat until the cotyledons rapidly expand with a pop. The bean is widely cultivated in the Andes, but almost unknown elsewhere. Objective & Methods: In this study, we characterized ten functional properties of a ñuña protein extract using standard food analysis methods. Results: The extract was similar to other legume protein extracts for many properties (amino acid profile, proximate analysis, yield, water absorption, color, isoelectric point, and thermogravimetric analysis). The electrophoretic analysis revealed that the sample was nearly pure phaseolin. Additionally, the ability to form foam and increase solution viscosity were comparatively low when contrasted to other extracts. Conclusion: These properties make ñuña protein extract useful as a nearly pure phaseolin nutrition enhancer in beverages where foaming and high viscosity are undesirable, such as in fortified beverages, drinkable yogurts, or protein supplements. The extract may also have relevance as a weight-loss supplement. Therefore, we expect that incorporating ñuña protein in processed foods would be a straightforward process.

Antecedentes: Los extractos proteicos de leguminosas son muy utilizados en la preparación y procesamiento de alimentos como agentes estabilizadores de espuma y viscosidad, así como potenciadores de palatabilidad y nutrición. Sin embargo, muchas proteínas de leguminosas procedentes de Sudamérica no han sido caracterizadas extensamente. Una de ellas es el frijol ñuña (Phaseolus vulgaris L.), el cual se cocina utilizando calor seco hasta que los cotiledones se expanden rápidamente y explotan. La ñuña se cultiva ampliamente en los Andes, pero es mayormente desconocida en otras partes del mundo. Objetivo y Métodos: En el presente estudio, caracterizamos diez propiedades funcionales de un extracto proteico de ñuña, utilizando métodos estándares para análisis de alimentos. Resultados: Varias propiedades del extracto analizado fueron similares a las de los extractos proteicos de otras leguminosas (perfil de aminoácidos, análisis proximal, rendimiento, absorción de agua, color, punto isoeléctrico y análisis termogravimétrico). El análisis electroforético reveló que la muestra es mayormente faseolina. Además, el extracto analizado presentó baja capacidad para formar espuma e incrementar viscosidad de una solución a comparación de los otros extractos. Conclusión: Los resultados obtenidos indican que el extracto proteico de ñuña, que es casi faseolina pura, puede ser muy útil como potenciador nutricional de bebidas en las que la espuma y alta viscosidad son indeseadas, como es el caso de bebidas fortificadas, yogures bebibles o suplementos proteicos. El extracto podría tener relevancia como suplemento para pérdida de peso. Por lo tanto, esperamos que el uso de proteína de ñuña sea un proceso sencillo en la industria de alimentos procesados.

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Helicobacter pylori (Marshall & Goodwin) is a widespread human pathogen that is acquiring resistance to the antibiotics used to treat it. This increasing resistance necessitates a continued search for new antibiotics. An antibiotic source that shows promise is animals whose immune systems must adapt to living in bacteria-laden conditions by producing antibacterial peptides or small molecules. Among these animals is the black soldier fly (BSF; Hermetia illucens Linnaeus), a Diptera that colonizes decomposing organic matter. In order to find anti-H. pylori peptides in BSF, larvae were challenged with Escherichia coli (Enterobacteriales: Enterobacteriaceae). Small peptides were extracted from hemolymph and purified using solid-phase extraction, molecular weight cutoff filtration and two rounds of preparative high performance liquid chromatography (HPLC). The anti-H. pylori fraction was followed through the purification process using the inhibition zone assay in brain-heart infusion agar, while peptides from uninoculated larvae had no activity. The inhibition halo of the active sample was comparable to the action of metronidazole in the inhibition zone assay. The purified sample contained four peptides with average masses of approximately 4.2 kDa that eluted together when analyzed by HPLC-mass spectrometry. The peptides likely have similar sequences, activity, and properties. Therefore, BSF produces inducible antibacterial peptides that have in vitro activity against H. pylori, which highlights BSF's position as an important target for further bioprospecting.

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the nigrostriatal pathway. The etiology of PD remains unclear and most cases are sporadic, however genetic mutations in more than 20 proteins have been shown to cause inherited forms of PD. Many of these proteins are linked to mitochondrial function, defects in which are a central characteristic of PD. Post-translational modifications (PTMs) allow rapid and reversible control over protein function. Largely focussing on mitochondrial dysfunction in PD, here we review findings on the PTMs phosphorylation, SUMOylation and ubiquitination that have been shown to affect PD-related proteins.

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