Genetic connections between neurological disorders and cholesterol metabolism
Open Access
- 1 September 2010
- journal article
- review article
- Published by Elsevier BV in Journal of Lipid Research
- Vol. 51 (9), 2489-2503
- https://doi.org/10.1194/jlr.r006338
Abstract
Cholesterol is an essential component of both the peripheral and central nervous systems of mammals. Over the last decade, evidence has accumulated that disturbances in cholesterol metabolism are associated with the development of various neurological conditions. In addition to genetically defined defects in cholesterol synthesis, which will be covered in another review in this Thematic Series, defects in cholesterol metabolism (cerebrotendinous xanthomatosis) and intracellular transport (Niemann Pick Syndrome) lead to neurological disease. A subform of hereditary spastic paresis (type SPG5) and Huntington's disease are neurological diseases with mutations in genes that are of importance for cholesterol metabolism. Neurodegeneration is generally associated with disturbances in cholesterol metabolism, and presence of the E4 isoform of the cholesterol transporter apolipoprotein E as well as hypercholesterolemia are important risk factors for development of Alzheimer's disease. In the present review, we discuss the links between genetic disturbances in cholesterol metabolism and the above neurological disorders. -Bjrkhem, I., V. Leoni, and S. Meaney. Genetic connections between neurological disorders and cholesterol metabolism. J. Lipid Res. 51: 2489-2503.Keywords
This publication has 144 references indexed in Scilit:
- ACAT1 gene ablation increases 24(S)-hydroxycholesterol content in the brain and ameliorates amyloid pathology in mice with ADProceedings of the National Academy of Sciences, 2010
- Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's DiseaseMolecular Therapy, 2010
- CYP7B1: One Cytochrome P450, Two Human Genetic Diseases, and Multiple Physiological FunctionsPublished by Elsevier BV ,2009
- 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A productionProceedings of the National Academy of Sciences of the United States of America, 2009
- Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's diseaseNature Genetics, 2009
- Wild-type but not mutant huntingtin modulates the transcriptional activity of liver X receptorsJournal of Medical Genetics, 2009
- NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomesProceedings of the National Academy of Sciences, 2008
- Sequence Alterations within CYP7B1 Implicate Defective Cholesterol Homeostasis in Motor-Neuron DegenerationAmerican Journal of Human Genetics, 2008
- Structural Basis of Sterol Binding by NPC2, a Lysosomal Protein Deficient in Niemann-Pick Type C2 DiseaseJournal of Biological Chemistry, 2007
- Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in BrainScience, 1997