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https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(20)30031-9 Highlights Orthogonal strategies such as drug repositioning, rational design, and high-throughput screening have identified molecules that target α‐synuclein (α-syn) aggregation, the central molecular event in Parkinson’s disease (PD). The anti-aggregation compounds under development target the complete spectrum of α-syn conformers through different mechanisms: monomer stabilization, prevention of dimer formation, stabilization or disruption of oligomers, avoidance of secondary nucleation, and dismantling of fibrils. The potential of particular molecules to halt neurodegeneration in PD is already being evaluated in clinical trials. If successful, they might benefit patients suffering from other α-synuclei

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  https://doi.org/10.3390/pharmaceutics12020157 (registering DOI) Abstract Inclusion bodies (IBs) are protein nanoclusters obtained during recombinant protein production processes, and several studies have demonstrated their potential as biomaterials for therapeutic protein delivery. Nevertheless, IBs have been, so far, exclusively sifted by their biological activity in vitro to be considered in further protein-based treatments in vivo. Matrix metalloproteinase-9 (MMP-9) protein, which has an important role facilitating the migration of immune cells, was used as model protein. The MMP-9 IBs were compared with their soluble counterpart and with MMP-9 encapsulated in polymeric-based micelles (PM) through ionic and covalent binding. The soluble MMP-9 and the MMP-9-ionic PM showed t

https://www.sciencedirect.com/science/article/pii/S1871678419302134?dgcid=coauthor https://doi.org/10.1016/j.nbt.2020.02.001 Abstract Efficient protocols for the production of recombinant proteins are indispensable for the development of the biopharmaceutical sector. Accumulation of recombinant proteins in naturally-occurring protein aggregates is detrimental to biopharmaceutical development. In recent years, the view of protein aggregates has changed with the recognition that they are a valuable source of functional recombinant proteins. In this study, bovine interferon-gamma (rBoIFN-γ) was engineered to enhance the formation of protein aggregates, also known as protein nanoparticles (NPs), by the addition of aggregation-prone peptides (APPs) in the generally recognized as safe (GR

Científicos españoles han desarrollado un nuevo fármaco que ataca el cáncer a través de nanopartículas. Además de reducir el tumor, éstas eliminan las células madre metastásicas y previenen así la metástasis en un modelo de cáncer colorrectal. El fármaco podría aplicarse en, al menos 23 tipos de cáncer, se administra por vía subcutánea y no tiene efectos adversos o tóxicos detectables. Investigadores del Hospital de Sant Pau, de la Universidad Autónoma de Barcelona (UAB) y el CIBER-BBN han comprobado que esta nueva forma farmacéutica, una vez administrada subcutáneamente, libera nanopartículas que se dirigen hacia los tejidos tumorales aumentando su captación en las células madre metastásicas. Según han explicado los investigadores, que publican su trabajo en la revista Advanced Material

Dr. Marc Martí Renom, antic doctorand a l'IBB i ara investigador ICREA al CNAG (https://www.icrea.cat/Web/ScientificStaff/Marc-Marti-Renom-573) (https://publons.com/researcher/2851715/marc-a-marti-renom/)                                                                         

https://doi.org/10.1016/j.celrep.2019.12.080 Highlights hnRNPDL requires both N- and C-terminal IDRs to phase separate The absence of N-terminal IDR facilitates aggregation The unique combination of IDRs in each isoform determines its cellular behavior D378N/H mutations accelerate hnRNPDL aggregation and compromise its solubility Summary Prion-like proteins form multivalent assemblies and phase separate into membraneless organelles. Heterogeneous ribonucleoprotein D-like (hnRNPDL) is a RNA-processing prion-like protein with three alternative splicing (AS) isoforms, which lack none, one, or both of its two disordered domains. It has been suggested that AS might regulate the assembly properties of RNA-processing proteins by controlling the incorporati...

https://elifesciences.org/articles/52978 Abstract Previous studies demonstrated importance of C-mannosylation for efficient protein secretion. To study its impact on protein folding and stability, we analyzed both C-mannosylated and non-C-mannosylated thrombospondin type 1 repeats (TSRs) of netrin receptor UNC-5. In absence of C-mannosylation, UNC-5 TSRs could only be obtained at low temperature and a significant proportion displayed incorrect intermolecular disulfide bridging, which was hardly observed when C-mannosylated. Glycosylated TSRs exhibited higher resistance to thermal and reductive denaturation processes, and the presence of C-mannoses promoted the oxidative folding of a reduced and denatured TSR in vitro. Molecular dynamics simulations supported the experimental studie...

https://www.tandfonline.com/doi/ref/10.1080/22221751.2019.1700762?scroll=top     ABSTRACT Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen Mycoplasma genitalium. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a f

  Cells 2020, 9(1), 145; https://doi.org/10.3390/cells9010145 Abstract Protein aggregation is associated with an increasing number of human disorders and premature aging. Moreover, it is a central concern in the manufacturing of recombinant proteins for biotechnological and therapeutic applications. Nevertheless, the unique architecture of protein aggregates is also exploited by nature for functional purposes, from bacteria to humans. The relevance of this process in health and disease has boosted the interest in understanding and controlling aggregation, with the concomitant development of a myriad of algorithms aimed to predict aggregation propensities. However, most of these programs are blind to the protein environment and, in particular, to the influence of the p