Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Sequence Alterations within CYP7B1 Implicate Defective Cholesterol Homeostasis in Motor-Neuron Degeneration
American Journal of Human Genetics, Volume 82, No. 2, Year 2008
Notification
URL copied to clipboard!
Description
The hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper-motor-neuron degenerative diseases characterized by selective axonal loss in the corticospinal tracts and dorsal columns. Although numerous mechanisms involving defective subcellular transportation, mitochondrial malfunction, and increased oxidative stress have been proposed, the pathogenic basis underlying the neuronal loss is unknown. We have performed linkage analysis to refine the extent of the SPG5 disease locus and conducted sequence analysis of the genes located within this region. This identified sequence alterations in the cytochrome P450-7B1 (CYP7B1) associated with this pure form of HSP. In the liver, CYP7B1 offers an alternative pathway for cholesterol degradation and also provides the primary metabolic route for the modification of dehydroepiandrosterone neurosteroids in the brain. These findings provide the first direct evidence of a pivotal role of altered cholesterol metabolism in the pathogenesis of motor-neuron degenerative disease and identify a potential for therapeutic intervention in this form of HSP. © 2008 The American Society of Human Genetics.
Authors & Co-Authors
Tsaousidou, Maria
United Kingdom, London
St George’s, University of London
Ouahchi, Karim
United States, Chicago
Northwestern University Feinberg School of Medicine
Warner, Tom
United Kingdom, London
Ucl Queen Square Institute of Neurology
Yang, Yi
United States, Chicago
Northwestern University Feinberg School of Medicine
Simpson, Michael A.
United Kingdom, London
St George’s, University of London
Laing, Nigel G.
Australia, Perth
The University of Western Australia
Wilkinson, Philip A.
United Kingdom, London
St George’s, University of London
United Kingdom, London
Ucl Queen Square Institute of Neurology
Madrid, Ricardo E.
United States, New York
New York State Institute for Basic Research in Developmental Disabilities
Patel, Heema
United Kingdom, London
St George’s, University of London
Hentati, F. F.
Tunisia, Tunis
Institut National de Neurologie Mongi-ben Hamida
Patton, Michael A.
United Kingdom, London
St George’s, University of London
Hentati, A.
Unknown Affiliation
Lamont, Phillipa J.
Australia, Perth
The University of Western Australia
Siddique, Teepu S.
United States, Chicago
Northwestern University Feinberg School of Medicine
Crosby, Andrew H.
United Kingdom, London
St George’s, University of London
Statistics
Citations: 15
Authors: 15
Affiliations: 6
Identifiers
Doi:
10.1016/j.ajhg.2007.10.001
ISSN:
00029297
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Randomised Control Trial