Delving into the Latest Updates on Centro de Biología Molecular Severo Ochoa with Synapse

概览

疾病领域	数量

肿瘤	1

排名前五的药物类型	数量

小分子化药	1

排名前五的靶点	数量

SYNGAP1	1

关联

1

项与 Centro de Biología Molecular Severo Ochoa 相关的药物

AIK-4

靶点

SYNGAP1

作用机制

SYNGAP1 inhibitors

在研机构

Allinky Biopharma SL [+1]

原研机构

Allinky Biopharma SL

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

1

项与 Centro de Biología Molecular Severo Ochoa 相关的临床试验

NCT02243683 / Completed临床1期

A Randomized, Placebo Controlled, Double Blind, Dose Escalating, Crossover, Safety and Pharmacokinetic Study of AX-024.HCl in Healthy Male Subjects

The purpose of this study is to determine the toxicity, tolerability and safety of single ascending doses of AX-024.HCl in healthy male subjects.

开始日期2014-09-01

申办/合作机构

Artax Biopharma, Inc.

[+3]

100 项与 Centro de Biología Molecular Severo Ochoa 相关的临床结果

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0 项与 Centro de Biología Molecular Severo Ochoa 相关的专利（医药）

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1,677

项与 Centro de Biología Molecular Severo Ochoa 相关的文献（医药）

2024-12-31·RNA Biology

Alternative splicing events driven by altered levels of GEMIN5 undergo translation

Article

作者: Martinez-Salas, Encarnacion ; Oliveros, Juan Carlos ; Abellan, Salvador ; Garcia-Martin, Juan Antonio ; Francisco-Velilla, Rosario

GEMIN5 is a multifunctional protein involved in various aspects of RNA biology, including biogenesis of snRNPs and translation control. Reduced levels of GEMIN5 confer a differential translation to selective groups of mRNAs, and biallelic variants reducing protein stability or inducing structural conformational changes are associated with neurological disorders. Here, we show that upregulation of GEMIN5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq identification of the mRNAs associated with polysomes in cells with high levels of GEMIN5 revealed that a significant fraction of the differential AS events undergo translation. The association of mRNAs with polysomes was dependent on the type of AS event, being more frequent in the case of exon skipping. However, there were no major differences in the percentage of genes showing open-reading frame disruption. Importantly, differential AS events in mRNAs engaged in polysomes, eventually rendering non-functional proteins, encode factors controlling cell growth. The broad range of mRNAs comprising AS events engaged in polysomes upon GEMIN5 upregulation supports the notion that this multifunctional protein has evolved as a gene expression balancer, consistent with its dual role as a member of the SMN complex and as a modulator of protein synthesis, ultimately impinging on cell homoeostasis.

2024-12-01·Clinical Proteomics

Proteomic snapshot of saliva samples predicts new pathways implicated in SARS-CoV-2 pathogenesis

Article

作者: Sanchez-Carrillo, Sergio ; Fátima, Santos Milhano ; Jiménez, Daniel ; Bargiela, Rafael ; Martínez-Sanz, Javier ; Moreno, Elena ; Sánchez-Conde, Matilde ; Corrales, Fernando ; Vizcarra, Pilar ; Ron, Raquel ; Moreno, Santiago ; Serrano-Villar, Sergio ; Ciordia, Sergio ; Ferrer, Manuel

AbstractBackgroundInformation on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients.MethodsWe compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5).ResultsBy performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group.ConclusionOur study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.Graphical Abstract

2024-12-01·Cellular and Molecular Life Sciences

Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm

Article

作者: Sarmiento-Jiménez, Jorge ; Castillo-Mancho, Vicente ; Culi, Joaquim ; Ruiz-Gómez, Mar ; Atienza-Manuel, Alexandra

AbstractBlood ultrafiltration in nephrons critically depends on specialized intercellular junctions between podocytes, named slit diaphragms (SDs). Here, by studying a homologous structure found in Drosophila nephrocytes, we identify the phospholipid scramblase Scramb1 as an essential component of the SD, uncovering a novel link between membrane dynamics and SD formation. In scramb1 mutants, SDs fail to form. Instead, the SD components Sticks and stones/nephrin, Polychaetoid/ZO-1, and the Src-kinase Src64B/Fyn associate in cortical foci lacking the key SD protein Dumbfounded/NEPH1. Scramb1 interaction with Polychaetoid/ZO-1 and Flotillin2, the presence of essential putative palmitoylation sites and its capacity to oligomerize, suggest a function in promoting SD assembly within lipid raft microdomains. Furthermore, Scramb1 interactors as well as its functional sensitivity to temperature, suggest an active involvement in membrane remodeling processes during SD assembly. Remarkably, putative Ca2+-binding sites in Scramb1 are essential for its activity raising the possibility that Ca2+ signaling may control the assembly of SDs by impacting on Scramb1 activity.

100 项与 Centro de Biología Molecular Severo Ochoa 相关的药物交易

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100 项与 Centro de Biología Molecular Severo Ochoa 相关的转化医学

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