TY - JOUR
T1 - Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease
AU - Zigdon, Hila
AU - Meshcheriakova, Anna
AU - Farfel-Becker, Tamar
AU - Volpert, Giora
AU - Sabanay, Helena
AU - Futerman, Anthony H.
N1 - Pfizer; Minerva Foundation; Children's Gaucher Research Fund; Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of ScienceThis work was supported by an Investigator-Initiated Research (IIR) grant from Pfizer, by the Minerva Foundation and by the Children's Gaucher Research Fund. We thank Vladimir Kiss for help with confocal microscopy, Haya Avital for help with graphics and Juan Castro and Silvana Zanlungo for providing NPC mouse brains. Electron microscopy studies were supported in part by the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science. AHF is the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science. This work was supported by an Investigator-Initiated Research (IIR) grant from Pfizer, by the Minerva Foundation and by the Children's Gaucher Research Fund. We thank Vladimir Kiss for help with confocal microscopy, Haya Avital for help with graphics and Juan Castro and Silvana Zanlungo for providing NPC mouse brains. Electron microscopy studies were supported in part by the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science. AHF is the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science.
PY - 2017/3
Y1 - 2017/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85013919678&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.12591
DO - 10.1002/1873-3468.12591
M3 - مقالة
SN - 0014-5793
VL - 591
SP - 774
EP - 783
JO - FEBS Letters
JF - FEBS Letters
IS - 5
ER -