title: The pathological roles of ganglioside metabolism in Alzheimer's disease: effects of gangliosides on neurogenesis.
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.
authors.affiliation: Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, 15th street, Augusta, GA 30912, USA.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ariga
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Wakade
authors.forename: Robert K
authors.initials: RK
authors.lastname: Yu