title: Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.
abstract: In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD.
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Zigdon
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Meshcheriakova
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Farfel-Becker
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Giora
authors.initials: G
authors.lastname: Volpert
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Helena
authors.initials: H
authors.lastname: Sabanay
authors.affiliation: Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Futerman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005776:Gaucher Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005962:Glucosylceramidase / Q000172:deficiency / Q000235:genetics; D005963:Glucosylceramides / Q000378:metabolism*; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D013997:Time Factors; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D018955:CD36 Antigens; D005962:Glucosylceramidase; D005963:Glucosylceramides; D051907:Lysosomal Membrane Proteins; D014404:Tubulin; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C489452:Scarb2 protein, mouse
keywords: Gaucher disease; glucosylceramide; lysosomes; neurons; neuropathology; paclitaxel