title: Monogenic neurological disorders of sphingolipid metabolism.
abstract: Sphingolipids comprise a wide variety of molecules containing a sphingoid long-chain base that can be N-acylated. These lipids are particularly abundant in the central nervous system, being membrane components of neurons as well as non-neuronal cells. Direct evidence that these brain lipids play critical functions in brain physiology is illustrated by the dramatic consequences of genetic disturbances of their metabolism. Inherited defects of both synthesis and catabolism of sphingolipids are now identified in humans. These monogenic disorders are due to mutations in the genes encoding for the enzymes that catalyze either the formation or degradation of simple sphingolipids such as ceramides, or complex sphingolipids like glycolipids. They cause varying degrees of central nervous system dysfunction, quite similarly to the neurological disorders induced in mice by gene disruption of the corresponding enzymes. Herein, the enzyme deficiencies and metabolic alterations that underlie these diseases are reviewed. Their possible pathophysiological mechanisms and the functions played by sphingolipids one can deduce from these conditions are discussed. This article is part of a Special Issue entitled Brain Lipids.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France; Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France.
authors: Frédérique
authors: F
authors: Sabourdy
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France; Service de Médecine Interne, CHU Purpan, Toulouse, France.
authors: Leonardo
authors: L
authors: Astudillo
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France.
authors: Céline
authors: C
authors: Colacios
authors: Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France.
authors: Patricia
authors: P
authors: Dubot
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France.
authors: Marguerite
authors: M
authors: Mrad
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France.
authors: Bruno
authors: B
authors: Ségui
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France.
authors: Nathalie
authors: N
authors: Andrieu-Abadie
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Toulouse, France; Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse-III Paul Sabatier, Toulouse, France; Laboratoire de Biochimie Métabolique, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France. Electronic address: thierry.levade@inserm.fr.
authors: Thierry
authors: T
authors: Levade
mesh_terms: D000818:Animals; D015870:Gene Expression; D006026:Glycoside Hydrolases / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D013107:Sphingolipids; D006026:Glycoside Hydrolases
keywords: Central nervous system; Ceramide; Ganglioside; Genetic defects; Glycolipid; Sphingolipidoses