title: Common and uncommon pathogenic cascades in lysosomal storage diseases.
abstract: Lysosomal storage diseases (LSDs), of which about 50 are known, are caused by the defective activity of lysosomal proteins, resulting in accumulation of unmetabolized substrates. As a result, a variety of pathogenic cascades are activated such as altered calcium homeostasis, oxidative stress, inflammation, altered lipid trafficking, autophagy, endoplasmic reticulum stress, and autoimmune responses. Some of these pathways are common to many LSDs, whereas others are only altered in a subset of LSDs. We now review how these cascades impact upon LSD pathology and suggest how intervention in the pathways may lead to novel therapeutic approaches.
authors.affiliation: From the Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Einat B
authors.initials: EB
authors.lastname: Vitner
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001327:Autoimmune Diseases / Q000453:epidemiology; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism; D005776:Gaucher Disease / Q000378:metabolism; D006801:Humans; D007790:Lactosylceramides / Q000378:metabolism; D016464:Lysosomal Storage Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D015703:Antigens, CD; D005609:Free Radicals; D005679:G(M3) Ganglioside; D007790:Lactosylceramides; D005678:G(M2) Ganglioside; C009744:CDw17 antigen; D002118:Calcium