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Aging Aug 2020Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized on chromosome 17 and encoding for acid alpha-1,4-glucosidase... (Review)
Review
Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, localized on chromosome 17 and encoding for acid alpha-1,4-glucosidase (GAA). Currently, more than 560 mutations spread throughout gene have been reported. GAA catalyzes the hydrolysis of α-1,4 and α-1,6-glucosidic bonds of glycogen and its deficiency leads to lysosomal storage of glycogen in several tissues, particularly in muscle. PD is a chronic and progressive pathology usually characterized by limb-girdle muscle weakness and respiratory failure. PD is classified as infantile and childhood/adult forms. PD patients exhibit a multisystemic manifestation that depends on age of onset.Early diagnosis is essential to prevent or reduce the irreversible organ damage associated with PD progression. Here, we make an overview of PD focusing on pathogenesis, clinical phenotypes, molecular genetics, diagnosis, therapies, autophagy and the role of miRNAs as potential biomarkers for PD.
Topics: Glycogen Storage Disease Type II; Humans; Phenotype
PubMed: 32745073
DOI: 10.18632/aging.103794 -
World Journal of Gastroenterology Jul 2023Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or... (Review)
Review
Glycogen storage diseases (GSDs), also referred to as glycogenoses, are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization. The overall estimated GSD incidence is 1 case per 20000-43000 live births. There are over 20 types of GSD including the subtypes. This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues. GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues. However, besides liver and skeletal muscle, depending on the affected enzyme and its expression in various tissues, multiorgan involvement including heart, kidney and/or brain may be seen. Although GSDs share similar clinical features to some extent, there is a wide spectrum of clinical phenotypes. Currently, the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch. In addition to nutritional interventions, pharmacological treatment, physical and supportive therapies, enzyme replacement therapy (ERT) and organ transplantation are other treatment approaches for both disease manifestations and long-term complications. The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy. Since early diagnosis and aggressive treatment are related to better prognosis, physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia, hepatomegaly, hypertransaminasemia, hyperlipidemia, exercise intolerance, muscle cramps/pain, rhabdomyolysis, and muscle weakness. Here, we aim to provide a comprehensive review of GSDs. This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
Topics: Humans; Glycogen Storage Disease; Liver; Glycogen; Muscle, Skeletal; Genetic Therapy
PubMed: 37476587
DOI: 10.3748/wjg.v29.i25.3932 -
Cells Jun 2021Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body... (Review)
Review
Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.
Topics: Caloric Restriction; Carbohydrate Metabolism; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lipolysis; Micronutrients; Signal Transduction
PubMed: 34199514
DOI: 10.3390/cells10061376 -
Journal of Extracellular Vesicles Feb 2022Mounting evidence suggests that storage has an impact on extracellular vesicles (EVs) properties. While -80°C storage is a widespread approach, some authors proposed...
Mounting evidence suggests that storage has an impact on extracellular vesicles (EVs) properties. While -80°C storage is a widespread approach, some authors proposed improved storage strategies with conflicting results. Here, we designed a systematic study to assess the impact of -80°C storage and freeze-thaw cycles on EVs. We tested the differences among eight storage strategies and investigated the possible fusion phenomena occurring during storage. EVs were collected from human plasma and murine microglia culture by size exclusion chromatography and ultracentrifugation, respectively. The analysis included: concentration, size and zeta potential (tunable resistive pulse sensing), contaminant protein assessment; flow cytometry for the analysis of two single fluorescent-tagged EVs populations (GFP and mCherry), mixed before preservation. We found that -80°C storage reduces EVs concentration and sample purity in a time-dependent manner. Furthermore, it increases the particle size and size variability and modifies EVs zeta potential, with a shift of EVs in size-charge plots. None of the tested conditions prevented the observed effects. Freeze-thaw cycles lead to an EVs reduction after the first cycle and to a cycle-dependent increase in particle size. With flow cytometry, after storage, we observed a significant population of double-positive EVs (GFP -mCherry ). This observation may suggest the occurrence of fusion phenomena during storage. Our findings show a significant impact of storage on EVs samples in terms of particle loss, purity reduction and fusion phenomena leading to artefactual particles. Depending on downstream analyses and experimental settings, EVs should probably be processed from fresh, non-archival, samples in majority of cases.
Topics: Animals; Chromatography, Gel; Extracellular Vesicles; Humans; Mice; Particle Size; Plasma; Ultracentrifugation
PubMed: 35102719
DOI: 10.1002/jev2.12162 -
Cell Feb 2020Lysosomal storage diseases (LSDs) represent a group of monogenic inherited metabolic disorders characterized by the progressive accumulation of undegraded substrates...
Lysosomal storage diseases (LSDs) represent a group of monogenic inherited metabolic disorders characterized by the progressive accumulation of undegraded substrates inside lysosomes, resulting in aberrant lysosomal activity and homeostasis. This SnapShot summarizes the intracellular localization and function of proteins implicated in LSDs. Common aspects of LSD pathogenesis and the major current therapeutic approaches are noted. To view this SnapShot, open or download the PDF.
Topics: Animals; Autophagy; Enzymes; Eukaryotic Cells; Homeostasis; Humans; Lysosomal Storage Diseases; Lysosomal Membrane Proteins; Lysosomes
PubMed: 32032518
DOI: 10.1016/j.cell.2020.01.017 -
Biomolecules Sep 2020Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to... (Review)
Review
Pompe disease, also known as glycogen storage disease type II, is caused by the lack or deficiency of a single enzyme, lysosomal acid alpha-glucosidase, leading to severe cardiac and skeletal muscle myopathy due to progressive accumulation of glycogen. The discovery that acid alpha-glucosidase resides in the lysosome gave rise to the concept of lysosomal storage diseases, and Pompe disease became the first among many monogenic diseases caused by loss of lysosomal enzyme activities. The only disease-specific treatment available for Pompe disease patients is enzyme replacement therapy (ERT) which aims to halt the natural course of the illness. Both the success and limitations of ERT provided novel insights in the pathophysiology of the disease and motivated the scientific community to develop the next generation of therapies that have already progressed to the clinic.
Topics: Autophagy; Enzyme Replacement Therapy; Genetic Therapy; Glycogen; Glycogen Storage Disease Type II; Humans; Lysosomal Storage Diseases; Lysosomes; Muscle, Skeletal; alpha-Glucosidases
PubMed: 32962155
DOI: 10.3390/biom10091339 -
Biotech (Basel (Switzerland)) Jun 2023The demand for data storage is growing at an unprecedented rate, and current methods are not sufficient to accommodate such rapid growth due to their cost, space... (Review)
Review
The demand for data storage is growing at an unprecedented rate, and current methods are not sufficient to accommodate such rapid growth due to their cost, space requirements, and energy consumption. Therefore, there is a need for a new, long-lasting data storage medium with high capacity, high data density, and high durability against extreme conditions. DNA is one of the most promising next-generation data carriers, with a storage density of 10¹⁹ bits of data per cubic centimeter, and its three-dimensional structure makes it about eight orders of magnitude denser than other storage media. DNA amplification during PCR or replication during cell proliferation enables the quick and inexpensive copying of vast amounts of data. In addition, DNA can possibly endure millions of years if stored in optimal conditions and dehydrated, making it useful for data storage. Numerous space experiments on microorganisms have also proven their extraordinary durability in extreme conditions, which suggests that DNA could be a durable storage medium for data. Despite some remaining challenges, such as the need to refine methods for the fast and error-free synthesis of oligonucleotides, DNA is a promising candidate for future data storage.
PubMed: 37366792
DOI: 10.3390/biotech12020044 -
Orphanet Journal of Rare Diseases Jun 2022Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and... (Review)
Review
BACKGROUND
Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs.
MAIN BODY
Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms, whose presentation can be similar. Compared to GSD type I and III, which are characterized by a more severe impact on metabolic and glycemic homeostasis, GSD type 0, VI, IX and XI are usually known to be responsive to the nutritional treatment for achieving a balanced metabolic homeostasis in the pediatric age. However, some patients can exhibit a more severe phenotype and an important progression of the liver and muscular disease. The effects of dietary adjustments in GSD type IV are encouraging, but data are limited.
CONCLUSIONS
Early diagnosis allows a good metabolic control, with improvement of quality of life and prognosis, therefore we underline the importance of building a proper knowledge among physicians about these rare conditions. Regular monitoring is necessary to restrain disease progression and complications.
Topics: Child; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Hypoglycemia; Liver; Quality of Life
PubMed: 35725468
DOI: 10.1186/s13023-022-02387-6 -
Trends in Biotechnology Jan 2021Microbial electrochemical technologies (METs) are promising for sustainable applications. Recently, electron storage during intermittent operation of electroactive... (Review)
Review
Microbial electrochemical technologies (METs) are promising for sustainable applications. Recently, electron storage during intermittent operation of electroactive biofilms (EABs) has been shown to play an important role in power output and electron efficiencies. Insights into electron storage mechanisms, and the conditions under which these occur, are essential to improve microbial electrochemical conversions and to optimize biotechnological processes. Here, we discuss the two main mechanisms for electron storage in EABs: storage in the form of reduced redox active components in the electron transport chain and in the form of polymers. We review electron storage in EABs and in other microorganisms and will discuss how the mechanisms of electron storage can be influenced.
Topics: Bioelectric Energy Sources; Biofilms; Electrodes; Electrons; Oxidation-Reduction
PubMed: 32646618
DOI: 10.1016/j.tibtech.2020.06.006 -
Biomolecules Jun 2021Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe...
Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe intellectual disabilities, cardiac abnormalities, visceromegaly, and bone deformities to slowly progressive muscle weakness, respiratory insufficiency, eye defects (corneal clouding and retinal degeneration), and skin alterations [...].
Topics: Humans; Lysosomal Storage Diseases; Lysosomes
PubMed: 34208892
DOI: 10.3390/biom11070964