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Mechanisms of demyelination and neurodegeneration in globoid cell leukodystrophy
Author(s) -
Feltri M. Laura,
Weinstock Nadav I.,
Favret Jacob,
Dhimal Narayan,
Wrabetz Lawrence,
Shin Daesung
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.24008
Subject(s) - leukodystrophy , krabbe disease , biology , myelin , neuroscience , neurodegeneration , central nervous system , metachromatic leukodystrophy , lysosomal storage disease , sandhoff disease , peripheral nervous system , sphingolipid , immunology , disease , microbiology and biotechnology , pathology , medicine , gene , genetics , enzyme , biochemistry
Globoid cell leukodystrophy (GLD), also known as Krabbe disease, is a lysosomal storage disorder causing extensive demyelination in the central and peripheral nervous systems. GLD is caused by loss‐of‐function mutations in the lysosomal hydrolase, galactosylceramidase (GALC), which catabolizes the myelin sphingolipid galactosylceramide. The pathophysiology of GLD is complex and reflects the expression of GALC in a number of glial and neural cell types in both the central and peripheral nervous systems (CNS and PNS), as well as leukocytes and kidney in the periphery. Over the years, GLD has garnered a wide range of scientific and medical interests, especially as a model system to study gene therapy and novel preclinical therapeutic approaches to treat the spontaneous murine model for GLD. Here, we review recent findings in the field of Krabbe disease, with particular emphasis on novel aspects of GALC physiology, GLD pathophysiology, and therapeutic strategies.