Lysosomal sulfatases: a growing family*

2020 ◽  
Vol 477 (20) ◽  
pp. 3963-3983 ◽  
Author(s):  
Torben Lübke ◽  
Markus Damme
Keyword(s):  
Current Knowledge ◽  
Essential Feature ◽  
Hydrolytic Degradation ◽  
Lysosomal Storage Diseases ◽  
Cysteine Residue ◽  
Special Focus ◽  
Lysosomal Storage ◽  
Multisystemic Disorders ◽  
Eukaryotic Genomes ◽  
Review Current

Sulfatases constitute a family of enzymes that specifically act in the hydrolytic degradation of sulfated metabolites by removing sulfate monoesters from various substrates, particularly glycolipids and glycosaminoglycans. A common essential feature of all known eukaryotic sulfatases is the posttranslational modification of a critical cysteine residue in their active site by oxidation to formylglycine (FGly), which is mediated by the FGly-generating enzyme in the endoplasmic reticulum and is indispensable for catalytic activity. The majority of the so far described sulfatases localize intracellularly to lysosomes, where they act in different catabolic pathways. Mutations in genes coding for lysosomal sulfatases lead to an accumulation of the sulfated substrates in lysosomes, resulting in impaired cellular function and multisystemic disorders presenting as lysosomal storage diseases, which also cover the mucopolysaccharidoses and metachromatic leukodystrophy. Bioinformatics analysis of the eukaryotic genomes revealed, besides the well described and long known disease-associated sulfatases, additional genes coding for putative enzymes with sulfatases activity, including arylsulfatase G as well as the arylsulfatases H, I, J and K, respectively. In this article, we review current knowledge about lysosomal sulfatases with a special focus on the just recently characterized family members arylsulfatase G and arylsulfatase K.

scholarly journals Lysosome function in glomerular health and disease

2021 ◽  
Author(s):  
Catherine Meyer-Schwesinger
Keyword(s):  
Current Knowledge ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Membrane Repair ◽  
Glomerular Cell ◽  
Wide Range ◽  
Center Position ◽  
Health And Disease

AbstractThe lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

scholarly journals Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

2021 ◽  
Author(s):  
Andrés Felipe Leal ◽  
Diego A. Suarez ◽  
Olga Yaneth Echeverri-Peña ◽  
Sonia Luz Albarracín ◽  
Carlos Javier Alméciga-Díaz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Signaling ◽  
Current Knowledge ◽  
Lysosomal Storage Diseases ◽  
Ionic Channels ◽  
Lysosomal Storage ◽  
Regulatory Pathways ◽  
Structural Part ◽  
Health And Disease

Sphingolipids are lipids derived from an 18-carbons unsaturated amino alcohol, the sphingosine. Ceramide, sphingomyelins, sphingosine-1-phosphates, gangliosides and globosides, are part of this group of lipids that participate in important cellular roles such as structural part of plasmatic and organelle membranes maintaining their function and integrity, cell signaling response, cell growth, cell cycle, cell death, inflammation, cell migration and differentiation, autophagy, angiogenesis, immune system. The metabolism of these lipids involves a broad and complex network of reactions that convert one lipid into others through different specialized enzymes. Impairment of sphingolipids metabolism has been associated with several disorders, from several lysosomal storage diseases, known as sphingolipidoses, to polygenic diseases such as diabetes and Parkinson and Alzheimer diseases. Sphingolipids are mainly located in central nervous system, and their abundance and distribution depend on brain development state and cell type. Although several studies have expanded the knowledge about sphingolipids function both in health and disease, it is still necessary to continue their study to understand the cellular implications of novel sphingolipids. These studies will also contribute to the diagnosis and treatment of diseases in which these molecules are part of their pathophysiology. In this review, we summarize the main sphingolipid characteristics and current knowledge about the synthesis, catabolism, regulatory pathways, participation in action potential and ionic channels, among other relevant functions.

scholarly journals Therapeutic Approaches in Lysosomal Storage Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1775
Author(s):  
Carlos Fernández-Pereira ◽  
Beatriz San Millán-Tejado ◽  
María Gallardo-Gómez ◽  
Tania Pérez-Márquez ◽  
Marta Alves-Villar ◽  
...  
Keyword(s):  
Small Molecules ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Lysosomal Storage ◽  
Future Perspectives ◽  
Therapeutic Approaches ◽  
Lysosomal Function ◽  
Storage Diseases ◽  
Enzyme Replacement ◽  
Multisystemic Disorders

Lysosomal Storage Diseases are multisystemic disorders determined by genetic variants, which affect the proteins involved in lysosomal function and cellular metabolism. Different therapeutic approaches, which are based on the physiologic mechanisms that regulate lysosomal function, have been proposed for these diseases. Currently, enzyme replacement therapy, gene therapy, or small molecules have been approved or are under clinical development to treat lysosomal storage disorders. The present article reviews the main therapeutic strategies that have been proposed so far, highlighting possible limitations and future perspectives.

Electron Microscopy in the diagnosis of lysosomal storage diseases

1989 ◽  
Vol 47 ◽  
pp. 866-867
Author(s):  
Carole Vogler ◽  
Harvey S. Rosenberg
Keyword(s):  
Electron Microscopy ◽  
Lysosomal Enzyme ◽  
Rectal Mucosa ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Storage Material ◽  
Ultrastructural Examination ◽  
Blood Leukocytes ◽  
Storage Diseases

Diagnostic procedures for evaluation of patients with lysosomal storage diseases (LSD) seek to identify a deficiency of a responsible lysosomal enzyme or accumulation of a substance that requires the missing enzyme for degradation. Most patients with LSD have progressive neurological degeneration and may have a variety of musculoskeletal and visceral abnormalities. In the LSD, the abnormally diminished lysosomal enzyme results in accumulation of unmetabolized catabolites in distended lysosomes. Because of the subcellular morphology and size of lysosomes, electron microscopy is an ideal tool to study tissue from patients with suspected LSD. In patients with LSD all cells lack the specific lysosomal enzyme but the distribution of storage material is dependent on the extent of catabolism of the substrate in each cell type under normal circumstances. Lysosmal storages diseases affect many cell types and tissues. Storage material though does not accumulate in all tissues and cell types and may be different biochemically and morphologically in different tissues.Conjunctiva, skin, rectal mucosa and peripheral blood leukocytes may show ultrastructural evidence of lysosomal storage even in the absence of clinical findings and thus any of these tissues can be used for ultrastructural examination in the diagnostic evaluation of patients with suspected LSD. Biopsy of skin and conjunctiva are easily obtained and provide multiple cell types including endothelium, epithelium, fibroblasts and nerves for ultrastructural study. Fibroblasts from skin and conjunctiva can also be utilized for the initiation of tissue cultures for chemical assays. Brain biopsy has been largely replaced by biopsy of more readily obtained tissue and by biochemical assays. Such assays though may give equivical or nondiagnostic results and in some lysosomal storage diseases an enzyme defect has not yet been identified and diagnoses can be made only by ultrastructural examination.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

scholarly journals Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 95
Author(s):  
Daisuke Tokuhara ◽  
Norikatsu Hikita
Keyword(s):  
Cord Blood ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Current System ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Adult Humans ◽  
Neonates And Infants ◽  
Induced Immunity ◽  
Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

scholarly journals Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

2021 ◽  
Vol 22 (14) ◽  
pp. 7339
Author(s):  
Julia Leschik ◽  
Beat Lutz ◽  
Antonietta Gentile
Keyword(s):  
Major Depression ◽  
Adult Neurogenesis ◽  
Current Knowledge ◽  
Functional Relation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Special Focus ◽  
Extrinsic Cues ◽  
Health And Disease ◽  
Newborn Neurons

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

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