biostudies-literatureClaycomb KINICHD NIH HHSNINDS NIH HHSPHS HHS964-74https://www.ebi.ac.uk/biostudies/studies/S-EPMC4169335biostudies-literatureUnknown73(10)Globoid cell leukodystrophy (GLD), or Krabbe disease, is a rare and often fatal demyelinating disease caused by mutations in the galactocerebrosidase (galc) gene that result in accumulation of galactosylsphingosine (psychosine). We recently reported that the extracellular matrix (ECM) protease, matrix metalloproteinase-3, is elevated in GLD and that it regulates psychosine-induced microglial activation. Here, we examined central nervous system ECM component expression in human GLD patients and in the twitcher mouse model of GLD using immunohistochemistry. The influence of ECM proteins on primary murine microglial responses to psychosine was evaluated using ECM proteins as substrates and analyzed by quantitative real-time polymerase chain reaction, immunocytochemistry, and ELISA. FunctionalJournal of neuropathology and experimental neurologyAberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.PMC4169335N01-HD-9-0011R01 NS065808R03 NS078392NS078392RNS065808AJohnson KMCrocker SJNicaise AMSacino AVBongarzone ERSnyder EYGiampetruzzi AWBarbarese EClaycomb KIWinokur PNfalseAberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.Globoid cell leukodystrophy (GLD), or Krabbe disease, is a rare and often fatal demyelinating disease caused by mutations in the galactocerebrosidase (galc) gene that result in accumulation of galactosylsphingosine (psychosine). We recently reported that the extracellular matrix (ECM) protease, matrix metalloproteinase-3, is elevated in GLD and that it regulates psychosine-induced microglial activation. Here, we examined central nervous system ECM component expression in human GLD patients and in the twitcher mouse model of GLD using immunohistochemistry. The influence of ECM proteins on primary murine microglial responses to psychosine was evaluated using ECM proteins as substrates and analyzed by quantitative real-time polymerase chain reaction, immunocytochemistry, and ELISA. Functional2014-01-01T00:00:00Z2014 Oct2025-04-22T21:09:50.271Z2019-03-27T01:36:00ZS-EPMC41693352519205110.1097/NEN.000000000000011710.1097/nen.0000000000000117