J. Lipid Res. Please sign the JLR Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.R800007-JLR200 on March 11, 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
R800007-JLR200v1
49/6/1157    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Ariga, T.
Right arrow Articles by Yu, R. K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ariga, T.
Right arrow Articles by Yu, R. K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Lipid Research, Vol. 49, 1157-1175, June 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Sphingolipids. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease—a review1

Toshio Ariga*, Michael P. McDonald{dagger} and Robert K. Yu2,*

* Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912
{dagger} Departments of Neurology and Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163

1 This article is dedicated to the memory of Dr. Herbert E. Carter.

This study was supported by National Institutes of Health Grants AG-027199, NS-026994, and NS-011853 to R.K.Y. and AG-022439 to M.P.M.

Published, JLR Papers in Press, March 11, 2008.

2 To whom correspondence should be addressed. e-mail: RYU{at}MCG.EDU

Gangliosides are expressed in the outer leaflet of the plasma membrane of the cells of all vertebrates and are particularly abundant in the nervous system. Ganglioside metabolism is closely associated with the pathology of Alzheimer's disease (AD). AD, the most common form of dementia, is a progressive degenerative disease of the brain characterized clinically by progressive loss of memory and cognitive function and eventually death. Neuropathologically, AD is characterized by amyloid deposits or "senile plaques," which consist mainly of aggregated variants of amyloid β-protein (Aβ). Aβ undergoes a conformational transition from random coil to ordered structure rich in β-sheets, especially after addition of lipid vesicles containing GM1 ganglioside. In AD brain, a complex of GM1 and Aβ, termed "GAβ," has been found to accumulate. In recent years, Aβ and GM1 have been identified in microdomains or lipid rafts. The functional roles of these microdomains in cellular processes are now beginning to unfold. Several articles also have documented the involvement of these microdomains in the pathogenesis of certain neurodegenerative diseases, such as AD. A pivotal neuroprotective role of gangliosides has been reported in in vivo and in vitro models of neuronal injury, Parkinsonism, and related diseases. Here we describe the possible involvement of gangliosides in the development of AD and the therapeutic potentials of gangliosides in this disorder.

Supplementary key words lipid raft • microdomain • amyloid β-protein

Abbreviations: Aβ, amyloid β-protein; AD, Alzheimer's disease; apoE, apolipoprotein E; APP, amyloid precursor protein; BBB, blood-brain barrier; CNS, central nervous system; CSF, cerebrospinal fluid; Ctxb, cholera toxin B-subunit; DAT, dementia of the Alzheimer type; DRM, detergent-resistant membrane; DS, Down syndrome; FL-Aβ, fluorescein-labeled Aβ; HPTLC, high-performance thin-layer chromatography; GAβ, GM1-bound Aβ complex; GD3S, GD3 synthase; GEM, glycolipid-enriched membrane; GPI, glycosylphosphatidylinositol; GSL, glycosphingolipid; LIGA 20, II3-Neu-5-AcGgOse4-2-D-erythro-1,3-dihydroxy-2-dichloroacetylamide-4-trans-octadecene; L-PDMP, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol; NGF, nerve growth factor; NPC, neuronal progenitor cell; PSEN, presenilin; SP, senile plaque; SPR, surface plasmon resonance; ST6Gal I, β-galactosidase {alpha}2,6-sialytransferase


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.