Publications by authors named "Garcia-Gimeno M"

Neuroinflammation and epilepsy are different pathologies, but, in some cases, they are so closely related that the activation of one of the pathologies leads to the development of the other. In this work, we discuss the three main cell types involved in neuroinflammation, namely (i) reactive astrocytes, (ii) activated microglia, and infiltration of (iii) peripheral immune cells in the central nervous system. Then, we discuss how neuroinflammation and epilepsy are interconnected and describe the use of different repurposing drugs with anti-inflammatory properties that have been shown to have a beneficial effect in different epilepsy models.

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Article Synopsis
  • Lafora disease (LD) is a neurological condition marked by progressive myoclonus epilepsy and the accumulation of insoluble glycogen forms, known as polyglucosan bodies (PGBs), in the brain.
  • Recent research shows that astrocytes, a type of brain cell, are the primary accumulators of PGBs, which may lead to their dysfunction and contribute to disease symptoms.
  • By using primary cultures of astrocytes from LD mice, researchers are exploring the metabolic changes and potential treatments to reduce PGB accumulation, finding that these cells exhibit increased glucose uptake and can help identify compounds that may alleviate PGB-related issues.
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Laforin and Malin are two proteins that are encoded by the genes EPM2A and EPM2B, respectively. Laforin is a glucan phosphatase and Malin is an E3-ubiquitin ligase, and these two proteins function as a complex. Mutations occurring at the level of one of the two genes lead to the accumulation of an aberrant form of glycogen meant to cluster in polyglucosans that go under the name of Lafora bodies.

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Aggregation of mutant huntingtin, because of an expanded polyglutamine track, underlies the cause of neurodegeneration in Huntington disease (HD). However, it remains unclear how some alterations at the cellular level lead to specific structural changes in HD brains. In this context, the neuroprotective effect of the activation of AMP-activated protein kinase (AMPK) appears to be a determinant factor in several neurodegenerative diseases, including HD.

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Lafora disease (LD) is a fatal childhood dementia characterized by progressive myoclonic epilepsy manifesting in the teenage years, rapid neurological decline, and death typically within ten years of onset. Mutations in either encoding the glycogen phosphatase laforin, or , encoding the E3 ligase malin, cause LD. Whole exome sequencing has revealed many variants associated with late-onset or slower disease progression.

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Metallosis is a well-known complication at the site of total hip and knee arthroplasty. Vascular involvement of this complication is rare and generally results from vascular compression by a mass or pseudotumor. In the present report, we have described a case of lower limb acute arterial ischemia due to arterial injury as a complication of metallosis with a fatal outcome.

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Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus.

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Lafora disease (LD) is a fatal rare type of progressive myoclonus epilepsy that appears during early adolescence. The disease is caused by mutations in EPM2A or EPM2B genes, which encode laforin, a glucan phosphatase, and malin, an E3-ubiquitin ligase, respectively. Although the exact roles of laforin and malin are still not well understood, it is known that they work as a complex in which laforin recruits targets that will be ubiquitinated by malin.

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Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g.

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Neuroinflammation and epilepsy are interconnected. Brain inflammation promotes neuronal hyper-excitability and seizures, and dysregulation in the glia immune-inflammatory function is a common factor that predisposes or contributes to the generation of seizures. At the same time, acute seizures upregulate the production of pro-inflammatory cytokines in microglia and astrocytes, triggering a downstream cascade of inflammatory mediators.

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Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing.

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Huntington disease is a neurodegenerative condition for which there is no cure to date. Activation of AMP-activated protein kinase has previously been shown to be beneficial in in vitro and in vivo models of Huntington's disease. Moreover, a recent cross-sectional study demonstrated that treatment with metformin, a well-known activator of this enzyme, is associated with better cognitive scores in patients with this disease.

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Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named Lafora bodies (LBs). LD is caused by mutations in the gene, encoding the dual phosphatase laforin, or the gene, encoding the E3-ubiquitin ligase malin.

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Lafora disease (LD, OMIM 254780) is a rare disorder characterized by epilepsy and neurodegeneration leading patients to a vegetative state and death, usually within the first decade from the onset of the first symptoms. In the vast majority of cases LD is related to mutations in either the EPM2A gene (encoding the glucan phosphatase laforin) or the EPM2B gene (encoding the E3-ubiquitin ligase malin). In this work, we characterize the mutations present in the EPM2A gene in a patient displaying a slow progression form of the disease.

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Mammalian AMP-activated protein kinase (AMPK) is a Ser/Thr protein kinase that acts as a crucial energy sensor in the cell. Since AMPK plays a key role in a multitude of different pathways in the cell, major efforts have been concentrated to elucidate its signaling network, mainly by the identification of AMPK downstream targets. In this chapter we describe a yeast two-hybrid method for the direct evaluation of the interaction between an AMPK subunit and putative substrates.

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Lafora disease (LD) is a fatal form of progressive myoclonus epilepsy characterized by the accumulation of insoluble poorly branched glycogen-like inclusions named Lafora bodies (LBs) in the brain and peripheral tissues. In the brain, since its first discovery in 1911, it was assumed that these glycogen inclusions were only present in affected neurons. Mouse models of LD have been obtained recently, and we and others have been able to report the accumulation of glycogen inclusions in the brain of LD animals, what recapitulates the hallmark of the disease.

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The spindle assembly checkpoint (SAC) generates a diffusible protein complex that prevents anaphase until all chromosomes are properly attached to spindle microtubules. A key step in SAC initiation is the recruitment of MAD1 to kinetochores, which is generally thought to be governed by the microtubule-kinetochore (MT-KT) attachment status. However, we demonstrate that the recruitment of MAD1 via BUB1, a conserved kinetochore receptor, is not affected by MT-KT interactions in human cells.

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Article Synopsis
  • A 78-year-old man with a history of abdominal infrarenal aortic surgery 20 years ago shows worsening aneurysm conditions, as seen in a CT scan.
  • The scan reveals degeneration in the infrarenal aorta, a left iliac aneurysm, and a new descending thoracic aneurysm near the aortic arch.
  • The surgical intervention was performed in two phases: first, both the thoracic and infrarenal aneurysms were treated with endoprostheses, and four years later, a branched iliac endograft addressed the iliac aneurysm.
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In yeast, SNF1 protein kinase is the orthologue of mammalian AMPK complex. It is a trimeric complex composed of Snf1 protein kinase (orthologue of AMPKα catalytic subunit), Snf4 (orthologue of AMPKγ regulatory subunit), and a member of the Gal83/Sip1/Sip2 family of proteins (orthologues of AMPKβ subunit) that act as scaffolds and also regulate the subcellular localization of the complex. In this chapter, we review the recent literature on the characteristics of SNF1 complex subunits, the structure and regulation of the activity of the SNF1 complex, its role at the level of transcriptional regulation of relevant target genes and also at the level of posttranslational modification of targeted substrates.

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Introduction: Expressing exogenous genes after naked DNA delivery into hepatocytes might achieve sustained and high expression of human proteins. Tail vein DNA injection is an efficient procedure for gene transfer in murine liver. Hydrodynamic procedures in large animals require organ targeting, and improve with liver vascular exclusion.

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AMP-activated protein kinase (AMPK) is a metabolic stress-sensing kinase. We previously showed that glucose deprivation induces autophosphorylation of AMPKβ at Thr-148, which prevents the binding of AMPK to glycogen. Furthermore, in MIN6 cells, AMPKβ1 binds to R6 (PPP1R3D), a glycogen-targeting subunit of protein phosphatase type 1 (PP1), thereby regulating the glucose-induced inactivation of AMPK.

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Protein phosphatase 1 (PP1) is one of the major protein phosphatases in eukaryotic cells. It plays a key role in regulating glycogen synthesis, by dephosphorylating crucial enzymes involved in glycogen homeostasis such as glycogen synthase (GS) and glycogen phosphorylase (GP). To play this role, PP1 binds to specific glycogen targeting subunits that, on one hand recognize the substrates to be dephosphorylated and on the other hand recruit PP1 to glycogen particles.

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Endoleak treatment after endovascular aneurysm repair (EVAR) can be difficult and complex. The key to success lies mostly in the accurate interpretation of imaging tests. We describe the case of a patient who was urgently operated on due to an episode of acute arterial ischemia in the left lower limb for stent-graft iliac limb thrombosis and a proximal type I endoleak.

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AMP-activated protein kinase (AMPK) is a sensor of energy status composed of a catalytic subunit (AMPKα), a scaffolding subunit (AMPKβ) and a regulatory subunit involved in nucleotide binding (AMPKγ). Activation of AMPK results in enhancement of catabolic processes and downregulation of anabolic pathways with the aim to equilibrate the energy status of the cell. The study of the regulation of the activity of the AMPK complex has been traditionally focused on modifications of AMPKα and AMPKγ subunits by post-translational changes (i.

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Protein phosphatase type 1 (PP1) plays a major role in the regulation of glycogen biosynthesis. PP1 is recruited to sites of glycogen formation by its binding to specific targeting subunits. There, it dephosphorylates different enzymes involved in glycogen homeostasis leading to an activation of glycogen biosynthesis.

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