Document Detail


CRASH syndrome: does it teach us about neurotrophic functions of cell adhesion molecules?
MedLine Citation:
PMID:  20817921     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
L1 cell adhesion molecule is a transmembrane glycoprotein of the immunoglobulin superfamily. L1 plays essential roles in normal development of the nervous system, and the mutations in the L1 gene are responsible for CRASH syndrome, a very rare inherited disorder characterized by corpus callosum hypoplasia, mental retardation, adducted thumbs, spastic paraplegia, and hydrocephalus. Here it is hypothesized that in the normal nervous system, the synthesis and neurotrophic function of L1 is controlled by a positive feedback loop, which consists of L1, L1 sheddases, gamma-secretase, L1 extracellular domain (L1ED), L1 cytoplasmic domain (L1CD), and transcriptional factor Pax6. The mutations in L1ED or L1CD will disrupt this feedback loop and inhibit the synthesis and neurotrophic function of L1, therefore contributing to the severe phenotypes in CRASH syndrome. Supported by several lines of experimental evidence, this hypothesis has important implications for the therapy of CRASH syndrome by guiding the development of novel strategies to restore this positive feedback loop to recover the normal function of L1 in CRASH patients.
Authors:
Ling Zhang
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry     Volume:  16     ISSN:  1089-4098     ISO Abbreviation:  Neuroscientist     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2011-01-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504819     Medline TA:  Neuroscientist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  470-4     Citation Subset:  IM    
Affiliation:
Department of Neurology, Zhongda Hospital, Southeast University, Nanjing, China. zhangling9@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Eye Proteins / genetics,  metabolism
Homeodomain Proteins / genetics,  metabolism
Humans
Mental Retardation / genetics,  metabolism
Neural Cell Adhesion Molecule L1 / genetics,  metabolism*
Paired Box Transcription Factors / genetics,  metabolism
Presenilins / genetics,  metabolism
Repressor Proteins / genetics,  metabolism
Spastic Paraplegia, Hereditary / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Eye Proteins; 0/Homeodomain Proteins; 0/Neural Cell Adhesion Molecule L1; 0/PAX6 protein; 0/Paired Box Transcription Factors; 0/Presenilins; 0/Repressor Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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