The Pathological Roles of Ganglioside Metabolism in Alzheimer's Disease: Effects of Gangliosides on Neurogenesis

Hdl Handle:
http://hdl.handle.net/10675.2/628
Title:
The Pathological Roles of Ganglioside Metabolism in Alzheimer's Disease: Effects of Gangliosides on Neurogenesis
Authors:
Ariga, Toshio; Wakade, Chandramohan; Yu, Robert K.
Abstract:
Conversion of the soluble, nontoxic amyloid β-protein (Aβ) into an aggregated, toxic form rich in β-sheets is a key step in the onset of Alzheimer’s disease (AD). It has been suggested that Aβ induces changes in neuronal membrane fluidity as a result of its interactions with membrane components such as cholesterol, phospholipids, and gangliosides. Gangliosides are known to bind Aβ. A complex of GM1 and Aβ, termed “GAβ”, has been identified in AD brains. Abnormal ganglioside metabolism also may occur in AD brains. We have reported an increase of Chol-1α antigens, GQ1bα and GT1aα, in the brain of transgenic mouse AD model. GQ1bα and GT1aα exhibit high affinities to Aβs. The presence of Chol-1α gangliosides represents evidence for genesis of cholinergic neurons in AD brains. We evaluated the effects of GM1 and Aβ1–40 on mouse neuroepithelial cells. Treatment of these cells simultaneously with GM1 and Aβ1–40 caused a significant reduction of cell number, suggesting that Aβ1–40 and GM1 cooperatively exert a cytotoxic effect on neuroepithelial cells. An understanding of the mechanism on the interaction of GM1 and Aβs in AD may contribute to the development of new neuroregenerative therapies for this disorder.
Citation:
Int J Alzheimers Dis. 2011 Jan 9; 2011:193618
Issue Date:
9-Jan-2011
URI:
http://hdl.handle.net/10675.2/628
DOI:
10.4061/2011/193618
PubMed ID:
21274438
PubMed Central ID:
PMC3025365
Type:
Article
ISSN:
2090-0252
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorAriga, Toshioen_US
dc.contributor.authorWakade, Chandramohanen_US
dc.contributor.authorYu, Robert K.en_US
dc.date.accessioned2012-10-26T16:26:55Z-
dc.date.available2012-10-26T16:26:55Z-
dc.date.issued2011-01-9en_US
dc.identifier.citationInt J Alzheimers Dis. 2011 Jan 9; 2011:193618en_US
dc.identifier.issn2090-0252en_US
dc.identifier.pmid21274438en_US
dc.identifier.doi10.4061/2011/193618en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/628-
dc.description.abstractConversion of the soluble, nontoxic amyloid β-protein (Aβ) into an aggregated, toxic form rich in β-sheets is a key step in the onset of Alzheimer’s disease (AD). It has been suggested that Aβ induces changes in neuronal membrane fluidity as a result of its interactions with membrane components such as cholesterol, phospholipids, and gangliosides. Gangliosides are known to bind Aβ. A complex of GM1 and Aβ, termed “GAβ”, has been identified in AD brains. Abnormal ganglioside metabolism also may occur in AD brains. We have reported an increase of Chol-1α antigens, GQ1bα and GT1aα, in the brain of transgenic mouse AD model. GQ1bα and GT1aα exhibit high affinities to Aβs. The presence of Chol-1α gangliosides represents evidence for genesis of cholinergic neurons in AD brains. We evaluated the effects of GM1 and Aβ1–40 on mouse neuroepithelial cells. Treatment of these cells simultaneously with GM1 and Aβ1–40 caused a significant reduction of cell number, suggesting that Aβ1–40 and GM1 cooperatively exert a cytotoxic effect on neuroepithelial cells. An understanding of the mechanism on the interaction of GM1 and Aβs in AD may contribute to the development of new neuroregenerative therapies for this disorder.en_US
dc.rightsCopyright © 2011 Toshio Ariga et al.en_US
dc.subjectReview Articleen_US
dc.titleThe Pathological Roles of Ganglioside Metabolism in Alzheimer's Disease: Effects of Gangliosides on Neurogenesisen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3025365en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-
dc.contributor.corporatenameInstitute of Neuroscience-
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