title: My encounters with Krabbe disease: A personal recollection of a 40-Year journey with young colleagues.
abstract: In this hybrid of a personal essay and a subjective review, I am attempting to convey the sense of an adventure I myself experienced in exploring various aspects of Krabbe disease, which occupied a significant portion of my life as a biomedical researcher. This is meant to be a personal summary, and I have no pretense of this being an objective scholarly review. Since the first description of the disease by Krabbe 100 years ago, knowledge about the disease has advanced significantly. The main contributions from my laboratory, always the fruits of dedicated efforts of talented young colleagues, include the identification of the genetic defect as deficiency of galactosylceramidase, proposal of the psychosine hypothesis as the pathogenetic mechanism to explain the unique phenotypic characteristics of the disease, detailed delineations of the substrate specificities of the two lysosomal β-galactosidases, discovery of the twitcher mutant as a convenient and useful mouse model, and identification of saposin A as a specific galactosylceramide activator protein and as the second causative gene for globoid cell leukodystrophy. Now, attempts are being made in many laboratories for meaningful therapy, unthinkable when I started working on this disease. Despite these advances, there are still many unknowns and uncertainties about Krabbe disease waiting to be clarified. © 2016 Wiley Periodicals, Inc.
authors.affiliation: 92suzuki3@gmail.com, kunihiko-suzuki@umin.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001325:Autobiographies as Topic; D035843:Biomedical Research / Q000266:history*; D003299:Cooperative Behavior; D004195:Disease Models, Animal; D005698:Galactosylceramidase / Q000172:deficiency / Q000235:genetics; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics / Q000266:history; D051379:Mice
chemical_list: D005698:Galactosylceramidase
keywords: Krabbe; galactosylceramidase; galactosylceramide; globoid cell leukodystrophy; prosaposin; psychosine; saposin A; twitcher mouse