116 results match your criteria gα activation

Endolysosomal N-glycan processing is critical to attain the most active form of the enzyme acid alpha-glucosidase.

J Biol Chem 2021 Jan-Jun;296:100769. Epub 2021 May 8.

Discovery Science Division, Amicus Therapeutics, Inc., Philadelphia, Pennsylvania, USA. Electronic address:

Acid alpha-glucosidase (GAA) is a lysosomal glycogen-catabolizing enzyme, the deficiency of which leads to Pompe disease. Pompe disease can be treated with systemic recombinant human GAA (rhGAA) enzyme replacement therapy (ERT), but the current standard of care exhibits poor uptake in skeletal muscles, limiting its clinical efficacy. Furthermore, it is unclear how the specific cellular processing steps of GAA after delivery to lysosomes impact its efficacy. Read More

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Ganoderic Acid A Attenuates LPS-Induced Neuroinflammation in BV2 Microglia by Activating Farnesoid X Receptor.

Neurochem Res 2021 Jul 5;46(7):1725-1736. Epub 2021 Apr 5.

School of Medicine, Yunnan University, 2 Cuihu North Road, Kunming, 650091, Yunnan, People's Republic of China.

Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases. Microglia-mediated neuroinflammation have been proved to be the main reason for causing the neurodegenerative diseases. Ganoderic acid A (GAA), isolated from Ganoderma lucidum, showed anti-inflammatory effect in metabolism diseases. Read More

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Nuclear Factor Erythroid 2-Related Factor 2 Activation Might Mitigate Clinical Symptoms in Friedreich's Ataxia: Clues of an "Out-Brain Origin" of the Disease From a Family Study.

Front Neurosci 2021 23;15:638810. Epub 2021 Feb 23.

Unit of Muscular and Neurodegenerative Diseases, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.

Friedreich's ataxia (FRDA) is the most frequent autosomal recessive ataxia in western countries, with a mean age of onset at 10-15 years. Patients manifest progressive cerebellar and sensory ataxia, dysarthria, lower limb pyramidal weakness, and other systemic manifestations. Previously, we described a family displaying two expanded GAA alleles not only in the proband affected by late-onset FRDA but also in the two asymptomatic family members: the mother and the younger sister. Read More

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February 2021

Activation of FXR by ganoderic acid A promotes remyelination in multiple sclerosis via anti-inflammation and regeneration mechanism.

Biochem Pharmacol 2021 03 20;185:114422. Epub 2021 Jan 20.

Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China. Electronic address:

Multiple sclerosis (MS), as an inflammatory demyelinating disorder of central nervous system, is the leading cause of non-traumatic neurologic disability in young adults. The pathogenesis of MS remains unknown, however, a dysregulation of glia-neuroimmune signaling plays a key role during progressive disease stage. Most of the existing drugs are aimed at the immune system, but there is no approved drug by promoting remyelination after demyelination so far. Read More

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Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

INM-Leibniz Institute for New Materials, 66123 Saarbrücken, Germany.

The Ca selective channel ORAI1 and endoplasmic reticulum (ER)-resident STIM proteins form the core of the channel complex mediating store operated Ca entry (SOCE). Using liquid phase electron microscopy (LPEM), the distribution of ORAI1 proteins was examined at rest and after SOCE-activation at nanoscale resolution. The analysis of over seven hundred thousand ORAI1 positions revealed a number of ORAI1 channels had formed STIM-independent distinct supra-molecular clusters. Read More

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January 2021

An experimental aerosol air-agar interface mouse lymphoma assay methodology.

Mutat Res 2020 Aug - Sep;856-857:503230. Epub 2020 Jul 13.

British American Tobacco, R&D, Southampton, Hampshire, SO15 8TL, UK.

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. Read More

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November 2020

Single-Grain Gate-All-Around Si Nanowire FET Using Low-Thermal-Budget Processes for Monolithic Three-Dimensional Integrated Circuits.

Micromachines (Basel) 2020 Jul 30;11(8). Epub 2020 Jul 30.

Institute of Electronics Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.

We introduce a single-grain gate-all-around (GAA) Si nanowire (NW) FET using the location-controlled-grain technique and several innovative low-thermal budget processes, including green nanosecond laser crystallization, far-infrared laser annealing, and hybrid laser-assisted salicidation, that keep the substrate temperature (T) lower than 400 °C for monolithic three-dimensional integrated circuits (3D-ICs). The detailed process verification of a low-defect GAA nanowire and electrical characteristics were investigated in this article. The GAA Si NW FETs, which were intentionally fabricated within the controlled Si grain, exhibit a steeper subthreshold swing (S. Read More

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[Testicular injection of lipopolysaccharide: An effective method for establishing the mouse model of orchitis].

Zhonghua Nan Ke Xue 2019 Aug;25(8):675-680

Faculty of Pathology, Nanchang University School of Medicine, Nanchang, Jiangxi 330006, China.

Objective: To search for a method of establishing a reliable mouse model of orchitis and investigate the association of orchitis with the activation of the inflammasome.

Methods: We equally randomized 40 adult male KM mice into groups A (sham operation), B (intraperitoneal injection of lipopolysaccharide [LPS]), C (unilateral testicular injection of glacial acetic acid [GAA]), and D (unilateral testicular injection of LPS). At 3 weeks after modeling, we measured the sperm concentration and percentage of progressively motile sperm (PMS) in the epididymis by computer-assisted semen analysis, observed the pathological changes in the testis tissue by HE staining, and determined the expressions of the Caspase-1 and interleukin (IL)-1β proteins by Western blot. Read More

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The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich's Ataxia.

Int J Mol Sci 2020 01 30;21(3). Epub 2020 Jan 30.

Unit of Muscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.

Friedreich's ataxia (FA) is a trinucleotide repeats expansion neurodegenerative disorder, for which no cure or approved therapies are present. In most cases, GAA trinucleotide repetitions in the first intron of the gene are the genetic trigger of FA, determining a strong reduction of frataxin, a mitochondrial protein involved in iron homeostasis. Frataxin depletion impairs iron-sulfur cluster biosynthesis and determines iron accumulation in the mitochondria. Read More

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January 2020

Quercetin Synergistically Inhibit EBV-Associated Gastric Carcinoma with Extracts.

Molecules 2019 Oct 24;24(21). Epub 2019 Oct 24.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.

Mycotherapy has been shown to improve the overall response rate during cancer treatment and reduce some chemotherapy-related adverse events. is a traditional mushroom used for pharmaceutical purposes. extracts (GLE) showed potential antitumor activities against several cancers. Read More

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October 2019

Ultrastable Bimolecular G-Quadruplexes Programmed DNA Nanoassemblies for Reconfigurable Biomimetic DNAzymes.

ACS Nano 2019 10 9;13(10):11947-11954. Epub 2019 Oct 9.

Department of Chemistry , University of Science and Technology of China , 96 Jinzhai Road , Hefei , Anhui 230026 , China.

The relatively low stability and polymorphism of bimolecular G-quadruplexes (bi-G4s) are big difficulties that are faced in employing them to guide DNA assembly, as they are usually subject to a transformation into more stable tetramolecular or G-wire structures favored by K or Mg. Although bi-G4s benefit by additional duplex handles, a challenge remains in tailoring their intrinsic properties to resolve the above difficulties. Toward this challenge, here we engineer several ultrastable bi-G4s replacing their nucleotide loops with special mini-hairpins, which consist of a GAA loop and a short GC-paired stem. Read More

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October 2019

Intestinal autophagy links psychosocial stress with gut microbiota to promote inflammatory bowel disease.

Cell Death Dis 2019 09 30;10(6):391. Epub 2019 Sep 30.

Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai, China.

Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Read More

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September 2019

Restoring the regenerative balance in neuromuscular disorders: satellite cell activation as therapeutic target in Pompe disease.

Ann Transl Med 2019 Jul;7(13):280

Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Skeletal muscle is capable of efficiently regenerating after damage in a process mediated by tissue-resident stem cells called satellite cells. This regenerative potential is often compromised under muscle-degenerative conditions. Consequently, the damage produced during degeneration is not efficiently repaired and the balance between repair and damage is lost. Read More

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Molecular Mechanisms and Therapeutics for the GAA·TTC Expansion Disease Friedreich Ataxia.

Neurotherapeutics 2019 10;16(4):1032-1049

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, 92037, USA.

Friedreich ataxia (FRDA), the most common inherited ataxia, is caused by transcriptional silencing of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin. Currently, there is no approved therapy for this fatal disorder. Gene silencing in FRDA is due to hyperexpansion of the triplet repeat sequence GAA·TTC in the first intron of the FXN gene, which results in chromatin histone modifications consistent with heterochromatin formation. Read More

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October 2019

Newborn screening for Pompe disease in Japan: report and literature review of mutations in the GAA gene in Japanese and Asian patients.

J Hum Genet 2019 Aug 10;64(8):741-755. Epub 2019 May 10.

Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

A newborn screening program for Pompe disease using dried blood spots (DBSs) was initiated in Japan. Here, we summarized this screening program and described the results of the GAA gene analysis. From April 2013 to November 2016, 103,204 newborns were screened; 71 had low acid alpha-glucosidase (AαGlu) activity. Read More

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Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice.

Biosci Rep 2019 05 23;39(5). Epub 2019 May 23.

Department of Respiratory and Critical Care Medicine, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210002, China

The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Read More

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Ganoderic acid A alleviates hypoxia-induced apoptosis, autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways.

Phytother Res 2019 May 6;33(5):1448-1456. Epub 2019 Mar 6.

Department of Pediatrics, Jining No. 1 People's Hospital (East Branch), Jining, China.

Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia-ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia-treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Read More

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Salmeterol with Liver Depot Gene Therapy Enhances the Skeletal Muscle Response in Murine Pompe Disease.

Hum Gene Ther 2019 07 5;30(7):855-864. Epub 2019 Apr 5.

1Division of Medical Genetics, Department of Pediatrics, Duke University Medical School, Durham, North Carolina.

Gene therapy for Pompe disease with adeno-associated virus (AAV) vectors has advanced into early phase clinical trials; however, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up acid α-glucosidase (GAA), has impeded the efficacy of Pompe disease gene therapy. Long-acting selective β2 receptor agonists previously enhanced the CI-MPR expression in muscle. In this study we have evaluated the selective β2 agonist salmeterol in GAA knockout mice in combination with an AAV vector expressing human GAA specifically in the liver. Read More

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Ferroptosis as a Novel Therapeutic Target for Friedreich's Ataxia.

J Pharmacol Exp Ther 2019 04 11;369(1):47-54. Epub 2019 Jan 11.

Department of Pathology and Laboratory Medicine, Children's Hospital Philadelphia, Philadelphia, Pennsylvania (M.G.C., S.X., D.L., T.L., R.B.W.); The Penn Medicine/CHOP Center of Excellence for Friedreich's Ataxia Research, Philadelphia, Pennsylvania (M.G.C., S.X., D.L., T.L., R.B.W.); Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania (L.T., P.W.); Department of Chemistry (D.M.H.), and Perelman School of Medicine (R.B.W.), University of Pennsylvania, Philadelphia, Pennsylvania

Friedreich ataxia (FRDA) is a progressive neuro- and cardio-degenerative disorder characterized by ataxia, sensory loss, and hypertrophic cardiomyopathy. In most cases, the disorder is caused by GAA repeat expansions in the first introns of both alleles of the gene, resulting in decreased expression of the encoded protein, frataxin. Frataxin localizes to the mitochondrial matrix and is required for iron-sulfur-cluster biosynthesis. Read More

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[Cytokine-regulating activity of anti-virus preparation CelAgripus in Burkitt's lymphoma stable B-cell lines.]

Vopr Virusol 2019 ;64(4):165-172

National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Moscow, 123098, Russian Federation.

Introduction: Cytokines activated in response to immunosuppressive viral infections can directly or indirectly affect the neoplastic transformation of B cells. In this study, we studied a new substance designed to produce the antiviral drug CelAgrip (CA, CelAgripus), which exhibits interferon (IFN) and cytokine-inducing activity and, apparently, can be used as an activator of antiviral immunity. Purpose - is to evaluate the cytokine-regulating effect of CA in Burkitt's lymphoma (LB) cell lines latently infected with the Epstein-Barr virus (EBV). Read More

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Exosomes Derived from Human Primary and Metastatic Colorectal Cancer Cells Contribute to Functional Heterogeneity of Activated Fibroblasts by Reprogramming Their Proteome.

Proteomics 2019 04 31;19(8):e1800148. Epub 2019 Jan 31.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of activated fibroblasts that constitute a dominant cellular component of the tumor microenvironment (TME) performing distinct functions. Here, the role of tumor-derived exosomes (Exos) in activating quiescent fibroblasts into distinct functional subtypes is investigated. Proteomic profiling and functional dissection reveal that early- (SW480) and late-stage (SW620) colorectal cancer (CRC) cell-derived Exos both activated normal quiescent fibroblasts (α-SMA , CAV , FAP , VIM ) into CAF-like fibroblasts (α-SMA , CAV , FAP , VIM ). Read More

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Plasma Markers of Neurodegeneration Are Raised in Friedreich's Ataxia.

Front Cell Neurosci 2018 30;12:366. Epub 2018 Oct 30.

Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.

Friedreich's ataxia (FRDA) is the most common autosomal recessive ataxia. Disease-modifying treatments are not available yet; however, several compounds are currently under investigation. As a result, there is a growing need for the identification of robust and easily accessible biomarkers for the monitoring of disease activity and therapeutic efficacy. Read More

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October 2018

Satellite cells maintain regenerative capacity but fail to repair disease-associated muscle damage in mice with Pompe disease.

Acta Neuropathol Commun 2018 11 7;6(1):119. Epub 2018 Nov 7.

Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Pompe disease is a metabolic myopathy that is caused by glycogen accumulation as a result of deficiency of the lysosomal enzyme acid alpha glucosidase (GAA). Previously, we showed that adult muscle stem cells termed satellite cells are present at normal levels in muscle from patients with Pompe disease, but that these are insufficiently activated to repair the severe muscle pathology. Here we characterized the muscle regenerative response during disease progression in a mouse model of Pompe disease and investigated the intrinsic capacity of Gaa satellite cells to regenerate muscle damage. Read More

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November 2018

Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II).

Acta Neuropathol Commun 2018 10 31;6(1):116. Epub 2018 Oct 31.

PAnTher, INRA, École Nationale Vétérinaire, Agro-alimentaire et de l'alimentation Nantes-Atlantique (Oniris), Université Bretagne Loire (UBL), Nantes, F-44307, France.

Pompe disease, which is due to acid alpha-glucosidase deficiency, is characterized by skeletal muscle dysfunction attributed to the accumulation of glycogen-filled lysosomes and autophagic buildup. Despite the extensive tissue damages, a failure of satellite cell (SC) activation and lack of muscle regeneration have been reported in patients. However, the origin of this defective program is unknown. Read More

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October 2018

Functional and Structural Brain Damage in Friedreich's Ataxia.

Front Neurol 2018 6;9:747. Epub 2018 Sep 6.

Severe Developmental Disabilities Unit, Scientific Institute, IRCCS "Eugenio Medea", Conegliano, Italy.

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Read More

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September 2018

Guanidinoacetic Acid Regulates Myogenic Differentiation and Muscle Growth Through miR-133a-3p and miR-1a-3p Co-mediated Akt/mTOR/S6K Signaling Pathway.

Int J Mol Sci 2018 Sep 19;19(9). Epub 2018 Sep 19.

Farm Animal Genetic Resource Exploration and Innovation Key Laboratory of Sichuan Province, Chengdu 611130, China.

Guanidinoacetic acid (GAA), an amino acid derivative that is endogenous to animal tissues including muscle and nerve, has been reported to enhance muscular performance. MicroRNA (miRNA) is a post-transcriptional regulator that plays a key role in nutrient-mediated myogenesis. However, the effects of GAA on myogenic differentiation and skeletal muscle growth, and the potential regulatory mechanisms of miRNA in these processes have not been elucidated. Read More

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September 2018

Activating frataxin expression by single-stranded siRNAs targeting the GAA repeat expansion.

Bioorg Med Chem Lett 2018 09 21;28(17):2850-2855. Epub 2018 Jul 21.

Department of Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, United States; Department of Biochemistry, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, United States. Electronic address:

Friedreich's ataxia (FRDA) is an incurable neurodegenerative disorder caused by reduced expression of the mitochondrial protein frataxin (FXN). The genetic cause of the disease is an expanded GAA repeat within the FXN gene. Agents that increase expression of FXN protein are a potential approach to therapy. Read More

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September 2018

Association of Low Lysosomal Enzymes Activity With Brain Arterial Dilatation.

Stroke 2018 08;49(8):1977-1980

Department of Neurology, Columbia University Medical Center, New York, NY (C.L., O.A.L., C.W., S.F., K.M., U.J.K., R.N.A., J.G.).

Background and Purpose- Absent or diminished α-galactosidase A (GLA) and acid α-glucosidase (GAA) enzyme activity are core features of Fabry and Pompe disease, respectively. Patients with Fabry or Pompe disease may have dilated intracranial arteries but whether lower GLA or GAA enzyme activity relates to brain arterial dilatation in other populations is unknown. Methods- Participants included Parkinson disease patients and nonblood-related controls, whose GLA and GAA enzymatic activities were measured in dried blood spots. Read More

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Systemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease.

Hum Gene Ther 2019 01 25;30(1):57-68. Epub 2018 Jul 25.

1 Division of Pulmonary Medicine, Department of Pediatrics, University of Massachusetts Medical School, Worcester Massachusetts.

Pompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and the central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease, since a single systemic injection may correct both muscle and CNS pathologies. Read More

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January 2019

Evolved Cas9 variants with broad PAM compatibility and high DNA specificity.

Nature 2018 04 28;556(7699):57-63. Epub 2018 Feb 28.

Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

A key limitation of the use of the CRISPR-Cas9 system for genome editing and other applications is the requirement that a protospacer adjacent motif (PAM) be present at the target site. For the most commonly used Cas9 from Streptococcus pyogenes (SpCas9), the required PAM sequence is NGG. No natural or engineered Cas9 variants that have been shown to function efficiently in mammalian cells offer a PAM less restrictive than NGG. Read More

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