DSpace Angular :: Browsing by Author "Zanlungo Matsuhiro, Silvana"

Browsing by Author "Zanlungo Matsuhiro, Silvana"

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A Ribosomal Protein S10 Gene Is Found in the Mitochondrial Genome in Solanum Tuberosum
(1994) Zanlungo Matsuhiro, Silvana; Holuigue Barros, María Loreto; Jordana, Xavier
Abnormalities of lipid metabolism, gallstone disease and gallbladder function
(2011) Zanlungo Matsuhiro, Silvana; Miquel P., Juan Francisco; Rigotti Rivera, Attilio; Nervi, Flavio
Gallstone disease is highly prevalent with a complex and multifactorial pathogenesis. Gallstones are closely related to the metabolic syndrome associated disease conditions in which abnormal regulation of lipid metabolism secondary to insulin resistance plays a major pathogenic role. Insulin resistance increases biliary cholesterol secretion and affects gallbladder (GB) motility. Regulation of lipid metabolism and energy homeostasis is complex and the GB has been considered to have a minor regulatory role in both the intestinal absorption of lipids and metabolic homeostasis of the whole body. In fact, ablation of the GB does not affect nutrient absorption or the ability to lead a normal life. GB function regulates the cycling of bile salts through the enterohepatic circulation. Bile salts have important signaling effects that can affect whole body metabolic homeostasis. The GB and intestinal mucosa are rich in the hormone FGF15/19 and the receptor TGR5, which participate in metabolic regulation. Recent evidence supports the hypothesis that cholecystectomy may not be innocuous and that the GB has a significant role in the regulation of hepatic triglyceride metabolism. This article provides information regarding recent advances in the understanding of the interaction between regulation of lipid metabolism, insulin resistance, gallstone disease and GB function.
Adenovirus-mediated hepatic syndecan-1 overexpression induces hepatocyte proliferation and hyperlipidaemia in mice
(2007) Cortés, V.; Zanlungo Matsuhiro, Silvana; Brandan, Enrique; Rigotti Rivera, Attilio
Amyloid-beta oligomers synaptotoxicity: The emerging role of epha4/c-Abl signaling in Alzheimer's disease
(2018) Vargas, L. M.; Cerpa Nebott, Waldo Francisco; Munoz, F. J.; Zanlungo Matsuhiro, Silvana; Álvarez Rojas, Alejandra
Autophagy Induced by Toll-like Receptor Ligands Regulates Antigen Extraction and Presentation by B Cells
(MDPI, 2022) Acharya, Mridu; Bozo, Juan Pablo; Diaz Munoz, Jheimmy Mariana; Guzman, Fanny; Lagos Orellana, Jonathan Alexander; Sagadiev, Sara; Stefani, Caroline; Yuseff Sepulveda, María Isabel; Zanlungo Matsuhiro, Silvana
The engagement of B cells with surface-tethered antigens triggers the formation of an immune synapse (IS), where the local secretion of lysosomes can facilitate antigen uptake. Lysosomes intersect with other intracellular processes, such as Toll-like Rece
c-Abl activates RIPK3 signaling in Gaucher disease
(2021) Yañez Henríquez, María José; Campos, F.; Marín Marín, Tamara Alejandra; Klein Posternack, Andrés David; Futerman, A. H.; Álvarez, Alejandra R.; Zanlungo Matsuhiro, Silvana
Gaucher disease (GD) is caused by homozygous mutations in the GBA1 gene, which encodes the lysosomal β-glucosidase (GBA) enzyme. GD affects several organs and tissues, including the brain in certain variants of the disease. Heterozygous GBA1 variants are a major genetic risk factor for developing Parkinson's disease. The RIPK3 kinase is relevant in GD and its deficiency improves the neurological and visceral symptoms in a murine GD model. RIPK3 mediates necroptotic-like cell death: it is unknown whether the role of RIPK3 in GD is the direct induction of necroptosis or if it has a more indirect function by mediating necrosis-independent. Also, the mechanisms that activate RIPK3 in GD are currently unknown. In this study, we show that c-Abl tyrosine kinase participates upstream of RIPK3 in GD. We found that the active, phosphorylated form of c-Abl is increased in several GD models, including patient's fibroblasts and GBA null mice. Furthermore, its pharmacological inhibition with the FDA-approved drug Imatinib decreased RIPK3 signaling. We found that c-Abl interacts with RIPK3, that RIPK3 is phosphorylated at a tyrosine site, and that this phosphorylation is reduced when c-Abl is inhibited. Genetic ablation of c-Abl in neuronal GD and GD mice models significantly reduced RIPK3 activation and MLKL downstream signaling. These results showed that c-Abl signaling is a new upstream pathway that activates RIPK3 and that its inhibition is an attractive therapeutic approach for the treatment of GD.
c-Abl Inhibition Activates TFEB and Promotes Cellular Clearance in a Lysosomal Disorder
(2020) Contreras, P. S.; Tapia Ossa, Pablo José; González Hódar, Lila Alejandra; Peluso, I.; Soldati, C.; Valls Jiménez, Cristián; Balboa Castillo, Elisa Ivana; Castro Alonso, Juan Cristóbal; Leal Reyes, Nancy Valeria; Zanlungo Matsuhiro, Silvana; Napolitano, G.; Matarese, M.; Heras, M. L.; Martinez, A.; Platt, F. M.; Sobota, A.; Winter, D.; Klein, A. D.; Medina, D. L.; Ballabio, A.; Alvarez, A. R.
c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases
(2023) Gutiérrez García, Daniela A.; Chandía Cristi, América Valeska; Yanez, Maria Jose; Zanlungo Matsuhiro, Silvana; Álvarez Rojas, Alejandra
Our ability to learn and remember depends on the active formation, remodeling, and elimination of synapses. Thus, the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring. The structural reorganization of synaptic complexes, changes in actin cytoskeleton and organelle dynamics, as well as modulation of gene expression, determine synaptic plasticity. It has been proposed that dysregulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases. Much is known about downstream signaling of activated N-methyl-D-aspartate and a-amino-3-hydroxy5-methyl-4-isoazolepropionate receptors; however, other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory. The non-receptor tyrosine kinase c-Abl (ABL1) is a key signal transducer of intra and extracellular signals, and it shuttles between the cytoplasm and the nucleus. This review focuses on c-Abl and its synaptic and neuronal functions. Here, we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons, promoting the development of neurodegenerative diseases. Nevertheless, c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity, regulating dendritic spines remodeling and gene expression after cognitive training, and synaptic dysfunction and loss in neurodegenerative diseases. Thus, c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice, but its absence provides dendritic spines resiliency against damage. Therefore, the present review has been designed to elucidate the common links between c-Abl regulation of structural changes that involve the actin cytoskeleton and organelles dynamics, and the transcriptional program activated during synaptic plasticity. By summarizing the recent discoveries on c-Abl functions, we aim to provide an overview of how its inhibition could be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.
C-ABL kinase in Niemann Pick type a disease : its implication in the pathogenic mechanisms leading to autophagic flux alterations and neurodegeneration.
(2020) Marín Marín, Tamara Alejandra; Zanlungo Matsuhiro, Silvana; Pontificia Universidad Católica de Chile. Facultad de Medicina
Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative and autosomal recessive disorder. It is characterized by deficiency in acid sphingomyelinase (ASM) and accumulation of sphingomyelin and cholesterol in lysosomes. Unfortunately, there is no cure for patients who die between 2-3 years of age. Previously we described that the c-Abl proapoptotic signaling pathway is key in neuronal death in different neurodegenerative diseases, including lysosomal disorders. Furthermore, recent studies show a role for c-Abl in autophagy and cellular clearance, processes that depend on the lysosome, and are essential for keeping cellular homeostasis. Indeed, autophagy dysfunctions are involved in different pathologies, including neurodegenerative diseases. Considering these antecedents, we propose to evaluate if c-Abl is hyperactivated and modulates autophagy and cellular clearance in NPA disease. The hypothesis of this thesis is that c-Abl hyperactivation blocks the autophagy flux contributing to the neuronal pathogenesis in Niemann Pick type A disease. Our general aim is to determine if c-Abl hyperactivation blocks the autophagy flux contributing to the neuronal pathogenesis in Niemann Pick type A disease. The specific aims are: 1) To determine if the c-Abl signaling pathway is hyperactivated and participates in NPA disease neurodegeneration and 2) To evaluate if hyperactivation of the c-Abl signaling pathway inhibits autophagy flux in NPA models. We used several NPA models including; fibroblasts from NPA patients, Neural Stem Cells derived from these fibroblasts and a NPA mouse. In these models we modulated c-Abl activity and evaluated cell death, cerebellar inflammation and autophagy flux. Our results show that: i) c-Abl is hyperactivated and contributes to the neurodegeneration in in vitro and in vivo NPA models; ii) There are lysosomal and autophagy alterations in NPA models; iii) c-Abl inhibition induces autophagy and decreases lipid accumulation in in vitro NPA models; iv) c-Abl inhibition decreases neuronal death and inflammation at the cerebellum and improves locomotor function in NPA mice and v) the downregulated genes in NPA fibroblasts increase their expression upon Imatinib treatment. Interestingly, these genes are direct or indirectly related with autophagy. These results give new antecedents to understand the role of c-Abl in autophagy regulation and its contribution to the NPA disease pathogenic mechanisms. Additionally, these results allow us to propose c-Abl inhibitors as a therapeutic option for this disease.
c-Abl links APP-BACE1 interaction promoting APP amyloidogenic processing in Niemann-Pick type C disease
(2016) Yañez, M.; Belbin, O.; Estrada, L.; Leal, N.; Contreras, P.; Lleó, A.; Burgos, P.; Zanlungo Matsuhiro, Silvana; Álvarez Rojas, Alejandra
c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration
(De Gruyter, 2023) Martinez Saavedra, Alexis; Lamaizon Muñoz, Cristián Nicolás; Valls Jimenez, Cristián; Llambi, Fabien; Leal Reyes, Nancy Valeria; Fitzgerald, Patrick; Guy, Cliff; Kaminsk,i Marcin M.; Inestrosa Cantin, Nibaldo; van Zundert, Brigitte; Cancino, Gonzalo; Dulcey, Andrés E.; Zanlungo Matsuhiro, Silvana; Marugan, Juan J.; Hetz, Claudio; Green, Douglas R.; Alvarez Rojas, Alejandra
The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation.
c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration
(MDPI, 2023) Martinez Saavedra, Alexis; Lamaizon Muñoz, Cristián Nicolás; Valls Jimenez, Cristián; Llambi, Fabien; Leal Reyes, Nancy Valeria; Fitzgerald, Patrick; Guy, Cliff; Kaminsk,i Marcin M.; Inestrosa Cantin, Nibaldo; van Zundert, Brigitte; Cancino, Gonzalo; Dulcey, Andrés E.; Zanlungo Matsuhiro, Silvana; Marugan, Juan J.; Hetz, Claudio; Green, Douglas R.; Alvarez Rojas, Alejandra
The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation.
C-Abl Tyrosine Kinase Signaling: A New Player in AD Tau Pathology
(2011) Estrada, L.; Zanlungo Matsuhiro, Silvana; Álvarez Rojas, Alejandra
Cholinergic abnormalities, endosomal alterations and up-regulation of nerve growth factor signaling in Niemann-Pick Type C disease
(2012) Cabeza Huerta, Carolina Andrea; Figueroa, Alicia; Lazo Jerez, Oscar Marcelo; Galleguillos, Carolina; Pissani Alvear, Claudia; Klein, Andrés; Inestrosa Cantín, Nibaldo; Álvarez Rojas, Alejandra; Zanlungo Matsuhiro, Silvana; Bronfman C., Francisca; Gonzalez-Billault, Christian
Abstract Background Neurotrophins and their receptors regulate several aspects of the developing and mature nervous system, including neuronal morphology and survival. Neurotrophin receptors are active in signaling endosomes, which are organelles that propagate neurotrophin signaling along neuronal processes. Defects in the Npc1 gene are associated with the accumulation of cholesterol and lipids in late endosomes and lysosomes, leading to neurodegeneration and Niemann-Pick type C (NPC) disease. The aim of this work was to assess whether the endosomal and lysosomal alterations observed in NPC disease disrupt neurotrophin signaling. As models, we used i) NPC1-deficient mice to evaluate the central cholinergic septo-hippocampal pathway and its response to nerve growth factor (NGF) after axotomy and ii) PC12 cells treated with U18666A, a pharmacological cellular model of NPC, stimulated with NGF. Results NPC1-deficient cholinergic cells respond to NGF after axotomy and exhibit increased levels of choline acetyl transferase (ChAT), whose gene is under the control of NGF signaling, compared to wild type cholinergic neurons. This finding was correlated with increased ChAT and phosphorylated Akt in basal forebrain homogenates. In addition, we found that cholinergic neurons from NPC1-deficient mice had disrupted neuronal morphology, suggesting early signs of neurodegeneration. Consistently, PC12 cells treated with U18666A presented a clear NPC cellular phenotype with a prominent endocytic dysfunction that includes an increased size of TrkA-containing endosomes and reduced recycling of the receptor. This result correlates with increased sensitivity to NGF, and, in particular, with up-regulation of the Akt and PLC-γ signaling pathways, increased neurite extension, increased phosphorylation of tau protein and cell death when PC12 cells are differentiated and treated with U18666A. Conclusions Our results suggest that the NPC cellular phenotype causes neuronal dysfunction through the abnormal up-regulation of survival pathways, which causes the perturbation of signaling cascades and anomalous phosphorylation of the cytoskeleton.
Complement Component C3 Participates in Early Stages of Niemann-Pick C Mouse Liver Damage
(2020) Klein, A. D.; Vega, J. G. de la; Zanlungo Matsuhiro, Silvana
Deficiency of Niemann-Pick C1 protein protects against diet-induced gallstone formation in mice
(2010) Morales France, María Gabriela; Amigo Böker, Ludwig Peter; Balboa Castillo, Elisa Ivana; Acuña Aravena, Mariana Loreto; Castro, Juan; Molina, Héctor; Miquel P., Juan Francisco; Nervi, Flavio; Rigotti Rivera, Attilio; Zanlungo Matsuhiro, Silvana
Determinants of transhepatic cholesterol flux and their relevance for gallstone formation
(2009) Zanlungo Matsuhiro, Silvana; Rigotti Rivera, Attilio Gianpietro
Cholesterol available for bile secretion is controlled by a wide variety of proteins that mediate lipoprotein cholesterol uptake and cholesterol transport and metabolism in the liver. From a disease perspective, abnormalities in the transhepatic traffic of cholesterol from plasma into the bile may influence the risk of cholesterol gallstone formation. This review summarizes some recent progress in understanding the hepatic determinants of biliary cholesterol secretion and its potential pathogenic implications in cholesterol gallstone disease. This information together with new discoveries in this field may lead to improved risk evaluation, novel surrogate markers and earlier diagnosis, better preventive approaches and more effective pharmacological therapies for this prevalent human disease.
Disfunción mitocondrial en la enfermedad de Niemann-Pick tipo C : contribución del aumento de colesterol mitocondrial mediado por MLN64.
(2015) Balboa Castillo, Elisa Ivana; Zanlungo Matsuhiro, Silvana; Pontificia Universidad Católica de Chile. Facultad de Medicina
La enfermedad de Niemann-Pick tipo C (NPC) se caracteriza por la acumulación lisosomal de colesterol, presencia de estrés oxidativo y muerte celular. Los tejidos más afectados son el cerebro y el hígado. Hasta la fecha, no se ha determinado el o los mecanismos que producen la muerte celular en estos tejidos. Para tratar de entender estos mecanismos y dado que se ha demostrado la contribución del daño mitocondrial en otras enfermedades neurodegenerativas y con daño hepático nosotros proponemos estudiar el funcionamiento y la dinámica mitocondrial en modelos NPC y evaluar la contribución de la disfunción mitocondrial en el daño celular observado en la enfermedad. Las mitocondrias son esenciales para la integridad celular, por lo que su dinámica está estrechamente regulada. La dinámica mitocondrial abarca procesos de fusión, fisión, biogénesis y autofagia. En las células NPC se ha observado que existe un mayor contenido de colesterol en la membrana mitocondrial y que procesos importantes de la mitocondria están alterados, como la síntesis de ATP y la entrada de GSH a la mitocondria. Se ha descrito además alteraciones en la morfología mitocondrial en tejidos NPC. Nuestra hipótesis es que el aumento de colesterol en la membrana mitocondrial produce disfunción mitocondrial en las células NPC. Además proponemos que la proteína MLN64 mediaría el transporte de colesterol a las mitocondrias en células NPC. En conjunto estas alteraciones convergerían en una reducción en la producción de energía, aumento en la producción de ROS y en la demanda de energía de las células NPC.El objetivo principal de este trabajo es evaluar si el aumento de colesterol, mediado por la proteína MLN64, contribuye a la disfunción mitocondrial y su relevancia en la patogenia de la enfermedad NPC. Para evaluar esto en diferentes modelos modulamos los niveles de expresión de MLN64 y evaluamos la función mitocondrial en diferentes modelos celulares y en tejidos del ratón Npc1-/-. Para mejorar la función mitocondrial en células NPC y ratones Npc1-/- usamos GSH-EE como antioxidante y Piracetam, una droga que estimula la producción de ATP. Nuestros resultados muestran, en diferentes modelos celulares NPC, disminución en el potencial de membrana, aumento de la producción de superóxido mitocondrial, disminución de GSH y alteraciones en la morfología mitocondrial en comparación con las células control. Las alteraciones en la morfología se relacionaron con disminución y aumento en los niveles de la proteína de fusión MFN2 y a de la proteína de fisión FIS1, respectivamente. En el hígado de ratones Npc1-/- encontramos disminución en la actividad de la ATPasa lo que se relacionó con un aumento significativo en el contenido de colesterol mitocondrial.El tratamiento con Piracetam previno la pérdida del PMM y el aumento de producción de superóxido mitocondrial en células tratadas con U18, pero en ratones Npc1-/- no tuvo efectos positivos. El tratamiento con GSH-EE previno la pérdida de peso en ratones Npc1-/- hasta las 8 semanas. Sin embargo, no tuvo efectos positivos en el comportamiento locomotor y en la sobrevida. Las células NPC y el hígado del ratón Npc1-/- presentaron aumento de la expresión de MLN64. Al disminuir los niveles de MLN64 en células NPC se previno la pérdida del potencial de membrana y disminuyeron los niveles de ROS mitocondrial. En el hígado de los ratones Npc1-/- la disminución de MLN64 provocó disminución del contenido de colesterol libre total y sorprendentemente un aumento en el contenido de colesterol mitocondrial. Por otra parte, en las células que sobreexpresan MLN64 encontramos alteraciones en la función mitocondrial y cambios en la morfología mitocondrial, estos últimos, asociados a disminución en la expresión de MFN2. La sobreexpresión de MLN64 en hígado de ratones produjo un aumento significativo en los niveles de colesterol mitocondrial, disminución en la actividad de la ATPasa, alteraciones en el consumo de oxígeno, disminución en el contenido de GSH mitocondrial y disminución de MFN2.Los resultados obtenidos en este trabajo muestran que existen alteraciones en la función mitocondrial en la enfermedad NPC y sugieren que MLN64 estaría involucrado en estas alteraciones, ya que la sobreexpresión de MLN64, produce alteraciones en la función y dinámica mitocondrial similares a las observadas en modelos NPC. En este trabajo por primera vez se demostró que la expresión de MLN64 está aumentada en modelos NPC, lo que podría constituir un mecanismo patogénico en la enfermedad NPC. Los resultados obtenidos y antecedentes de la bibliografía sugieren que MLN64 participaría en la homeostasis celular del colesterol y favorecería la acumulación de colesterol en la mitocondria en la enfermedad NPC. La función de la proteína MLN64 no ha sido completamente dilucidada y no se puede descartar que MLN64 regule la función de otras proteínas transportadoras de colesterol que pueden favorecer el transporte de colesterol a la mitocondria. Las conclusiones de este trabajo es que en modelos NPC existen alteraciones en la función y en la morfología mitocondrial. Estas alteraciones estarían relacionadas a un aumento del contenido de colesterol mitocondrial mediado por MLN64 y a cambios en la expresión de proteínas reguladoras de los procesos de fusión y fisión mitocondrial. La importancia de este trabajo es que se demuestra que existe disfunción mitocondrial en la enfermedad de NPC y que esta disfunción podría estar relacionada al aumento de colesterol mitocondrial y al aumento de expresión de MLN64.
Disruption in connexin-based communication is associated with intracellular Ca²⁺ signal alterations in astrocytes from Niemann-Pick type C mice
(2013) Sáez Pedraza, Pablo José; Orellana Roca, Juan Andrés; Vega-Riveros, Natalia; Figueroa, Vania A.; Hernández Trejo, Diego Eduardo; Castro, Juan Francisco; Klein Posternack, Andrés David; Jean X. Jiang; Zanlungo Matsuhiro, Silvana; Sáez Carreño, Juan Carlos
Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1⁻/⁻) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1⁻/⁻ hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1⁻/⁻ astrocytes also showed more intracellular Ca²⁺ signal oscillations mediated by functional connexin 43 hemichannels and P2Y₁ receptors. Therefore, Npc1⁻/⁻ astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.
El síndrome metabólico: de factor agravante a principal factor de riesgo patogénico en diversas enfermedades crónicas
(2010) Von Bernhardi Montgomery, Rommy Edth B.; Zanlungo Matsuhiro, Silvana; Arrese Jiménez, Marco Antonio; Arteaga Llona, Antonio Alberto; Rigotti Rivera, Attilio Gianpietro
In recent years, a rapidly increasing number of studies have focused on the association between metabolic syndrome and several chronic diseases. However, it is difficult to determine a well defined pathogenic relationship, due to the etiological heterogeneity and comorbidities of these diseases. Research efforts are aiming to identify the convergent biological mechanisms that mediate the effects of hyperinsulinemia, hyperglycemia, dyslipidemia, and hypertension. All these conditions define the metabolic syndrome, that increases the risk for several diseases. The knowledge of these biological mechanisms associated with this syndrome will elucidate the pathogenic association between a variety of chronic diseases, including its pathogenic link with cardiovascular diseases and the most common forms of dementia. The development of new therapeutic and preventive strategies for these diseases will be a corollary of this research.

Browsing by Author "Zanlungo Matsuhiro, Silvana"

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