Lysosomal Storage Disorders

2021 ◽  
pp. 1106-1113
Author(s):  
Radhika Dhamija ◽  
Erin Conboy ◽  
Lily C. Wong-Kisiel
Keyword(s):  
Lysosomal Storage Diseases ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Activator Proteins ◽  
Autophagic Vacuoles ◽  
Enzyme Substrate ◽  
Membrane Bound ◽  
Considerable Morbidity ◽  
Storage Disorders

Lysosomes are membrane-bound organelles that degrade various macromolecules. Lysosomal storage diseases are a clinically, enzymatically, and genetically heterogeneous group of disorders resulting from intracellular accumulation of substrates. Mechanisms of lysosomal storage disorders include 1) primary deficiency of specific hydrolases; 2) defects in activator proteins required for enzyme-substrate interactions in posttranslational modification of enzymes or in transport of the substrate from lysosomes; and 3) abnormalities of fusion between autophagic vacuoles and lysosomes. Substrate accumulation is slowly progressive, leading to considerable morbidity and mortality.

scholarly journals Lysosomal storage disorders: The cellular impact of lysosomal dysfunction

2012 ◽  
Vol 199 (5) ◽  
pp. 723-734 ◽  
Author(s):  
Frances M. Platt ◽  
Barry Boland ◽  
Aarnoud C. van der Spoel
Keyword(s):  
Lysosomal Enzymes ◽  
Gene Mutations ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Lysosomal Dysfunction ◽  
Membrane Bound ◽  
Cellular Pathways ◽  
Normal Cellular Function ◽  
Lysosomal Proteins ◽  
Storage Disorders

Lysosomal storage diseases (LSDs) are a family of disorders that result from inherited gene mutations that perturb lysosomal homeostasis. LSDs mainly stem from deficiencies in lysosomal enzymes, but also in some non-enzymatic lysosomal proteins, which lead to abnormal storage of macromolecular substrates. Valuable insights into lysosome functions have emerged from research into these diseases. In addition to primary lysosomal dysfunction, cellular pathways associated with other membrane-bound organelles are perturbed in these disorders. Through selective examples, we illustrate why the term “cellular storage disorders” may be a more appropriate description of these diseases and discuss therapies that can alleviate storage and restore normal cellular function.

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 Potential resistance to SARS-CoV-2 infection in lysosomal storage disorders

2021 ◽  
Author(s):  
Maurizio Pieroni ◽  
Federico Pieruzzi ◽  
Renzo Mignani ◽  
Francesca Graziani ◽  
Iacopo Olivotto ◽  
...  
Keyword(s):  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Storage Disorders

scholarly journals Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maria De Risi ◽  
Michele Tufano ◽  
Filomena Grazia Alvino ◽  
Maria Grazia Ferraro ◽  
Giulia Torromino ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Sch 23390 ◽  
Lysosomal Storage Disorders ◽  
Dopamine Neurons ◽  
Therapeutic Effects ◽  
Lysosomal Storage ◽  
Cellular Models ◽  
Mps Ii ◽  
Mps Iiia ◽  
Storage Disorders

AbstractLysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

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