scholarly journals Ferroptosis and Its Modulation by Autophagy in Light of the Pathogenesis of Lysosomal Storage Diseases

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 365
Author(s):  
Karolina Pierzynowska ◽  
Estera Rintz ◽  
Lidia Gaffke ◽  
Grzegorz Węgrzyn
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Lysosomal Storage Diseases ◽  
Review Article ◽  
Lysosomal Storage ◽  
Ferrous Ions ◽  
Autophagy Flux ◽  
Considerable Contribution ◽  
Storage Diseases

Ferroptosis is one of the recently described types of cell death which is dependent on many factors, including the accumulation of iron and lipid peroxidation. Its induction requires various signaling pathways. Recent discovery of ferroptosis induction pathways stimulated by autophagy, so called autophagy-dependent ferroptosis, put our attention on the role of ferroptosis in lysosomal storage diseases (LSD). Lysosome dysfunction, observed in these diseases, may influence ferroptosis efficiency, with as yet unknown consequences for the function of cells, tissues, and organisms, due to the effects of ferroptosis on physiological and pathological metabolic processes. Modulation of levels of ferrous ions and enhanced oxidative stress, which are primary markers of ferroptosis, are often described as processes associated with the pathology of LSD. Inhibition of autophagy flux and resultant accumulation of autophagosomes in neuronopathic LSD may induce autophagy-dependent ferroptosis, indicating a considerable contribution of this process in neurodegeneration. In this review article, we describe molecular mechanisms of ferroptosis in light of LSD, underlining the modulation of levels of ferroptosis markers in these diseases. Furthermore, we propose a hypothesis about the possible involvement of autophagy-dependent ferroptosis in these disorders.

scholarly journals Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction

2016 ◽  
Vol 117 (2) ◽  
pp. 66-83 ◽  
Author(s):  
Priya S. Kishnani ◽  
Patricia I. Dickson ◽  
Laurie Muldowney ◽  
Jessica J. Lee ◽  
Amy Rosenberg ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Immune Tolerance Induction ◽  
Storage Diseases ◽  
Enzyme Replacement

Innate immune responses in the brain of sphingolipid lysosomal storage diseases

2015 ◽  
Vol 396 (6-7) ◽  
pp. 659-667 ◽  
Author(s):  
Einat B. Vitner ◽  
Anthony H. Futerman ◽  
Nick Platt
Keyword(s):  
Lysosomal Storage Diseases ◽  
Sandhoff Disease ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Lysosomal Storage ◽  
Lysosomal Hydrolases ◽  
Storage Diseases ◽  
Niemann Pick ◽  
The Brain

Abstract Lysosomal storage diseases (LSDs) are mainly caused by the defective activity of lysosomal hydrolases. A sub-class of LSDs are the sphingolipidoses, in which sphingolipids accumulate intra-cellularly. We here discuss the role of innate immunity in the sphingolipidoses, and compare the pathways of activation in two classical sphingolipidoses, namely Gaucher disease and Sandhoff disease, and in Niemann-Pick C disease, in which the main storage material is cholesterol but sphingolipids also accumulate. We discuss the mechanisms leading to neuroinflammation, and the different pathways of neuroinflammation in the different diseases, and suggest that intervention in these pathways may be a useful therapeutic approach to address these devastating human diseases.

The Emerging Role of the Pediatric Physical Therapist in Evaluation and Intervention for Individuals with Lysosomal Storage Diseases

2005 ◽  
Vol 17 (2) ◽  
pp. 128-139 ◽  
Author(s):  
Stephen M. Haley ◽  
Maria Fragala-Pinkham ◽  
Nancy K. Latham ◽  
Alison M. Skrinar ◽  
Deborah Cogswell
Keyword(s):  
Physical Therapist ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases

scholarly journals Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses

2020 ◽  
Vol 21 (9) ◽  
pp. 3194 ◽  
Author(s):  
Estera Rintz ◽  
Lidia Gaffke ◽  
Magdalena Podlacha ◽  
Joanna Brokowska ◽  
Zuzanna Cyske ◽  
...  
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Monogenic Disorders ◽  
Cellular Processes ◽  
Transcriptomic Changes ◽  
Molecular Pathomechanisms

Although mucopolysaccharidoses (MPS), inherited metabolic diseases from the group of lysosomal storage diseases (LSD), are monogenic disorders, recent studies indicated that their molecular mechanisms are complicated. Storage of glycosaminoglycans (GAGs), arising from a deficiency in one of the enzymes involved in the degradation of these compounds, is the primary cause of each MPS type. However, dysfunctions of various cellular organelles and disturbance of cellular processes have been reported which contribute considerably to pathomechanisms of the disease. Here, we present a complex transcriptomic analysis in which all types and subtypes of MPS were investigated, with special emphasis on genes related to cell activation processes. Complex changes in expression of these genes were found in fibroblasts of all MPS types, with number of transcripts revealing higher or lower levels (relative to control fibroblasts) between 19 and over 50, depending on MPS type. Genes in which expression was significantly affected in most MPS types code for proteins involved in following processes, classified according to Gene Ontology knowledge database: cell activation, cell growth, cell recognition, and cell division. Levels of some transcripts (including CD9, CLU, MME and others) were especially significantly changed (over five times relative to controls). Our results are discussed in the light of molecular pathomechanisms of MPS, indicating that secondary and/or tertiary changes, relative to GAG storage, might significantly modulate cellular dysfunctions and contribute to molecular mechanisms of the disease. This may influence the efficacy of various therapies and suggests why various treatments are not fully effective in improving the complex symptoms of MPS.

scholarly journals The role of automated analyzers in detecting abnormal granulation of leucocytes in lysosomal storage diseases: Maroteaux-Lamy disease

2013 ◽  
Vol 88 (6) ◽  
pp. 527-527 ◽  
Author(s):  
Elisa Piva ◽  
Michela Pelloso ◽  
Daniela Ciubotaru ◽  
Laura Penello ◽  
Alberto Burlina ◽  
...  
Keyword(s):  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases

scholarly journals Reconstruction of the Cytokine Signaling in Lysosomal Storage Diseases by Literature Mining and Network Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Silvia Parolo ◽  
Danilo Tomasoni ◽  
Pranami Bora ◽  
Alan Ramponi ◽  
Chanchala Kaddi ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Lysosomal Storage Diseases ◽  
Acid Sphingomyelinase ◽  
Cytokine Signaling ◽  
Literature Mining ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Inflammatory Signals

Lysosomal storage diseases (LSDs) are characterized by the abnormal accumulation of substrates in tissues due to the deficiency of lysosomal proteins. Among the numerous clinical manifestations, chronic inflammation has been consistently reported for several LSDs. However, the molecular mechanisms involved in the inflammatory response are still not completely understood. In this study, we performed text-mining and systems biology analyses to investigate the inflammatory signals in three LSDs characterized by sphingolipid accumulation: Gaucher disease, Acid Sphingomyelinase Deficiency (ASMD), and Fabry Disease. We first identified the cytokines linked to the LSDs, and then built on the extracted knowledge to investigate the inflammatory signals. We found numerous transcription factors that are putative regulators of cytokine expression in a cell-specific context, such as the signaling axes controlled by STAT2, JUN, and NR4A2 as candidate regulators of the monocyte Gaucher disease cytokine network. Overall, our results suggest the presence of a complex inflammatory signaling in LSDs involving many cellular and molecular players that could be further investigated as putative targets of anti-inflammatory therapies.

scholarly journals The Underexploited Role of Non-Coding RNAs in Lysosomal Storage Diseases

2016 ◽  
Vol 7 ◽  
Author(s):  
Matheus Trovão de Queiroz ◽  
Vanessa Gonçalves Pereira ◽  
Cinthia Castro do Nascimento ◽  
Vânia D’Almeida
Keyword(s):  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Non Coding Rnas

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.

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