The pathological roles of ganglioside metabolism in Alzheimer's disease

Effects of gangliosides on neurogenesis

Research output: Contribution to journalReview article

25 Citations (Scopus)

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 A 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 GT1a, in the brain of transgenic mouse AD model. GQ1bα and GT1a 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.

Original languageEnglish (US)
Article number193618
JournalInternational Journal of Alzheimer's Disease
DOIs
StatePublished - Mar 7 2011

Fingerprint

Gangliosides
Neurogenesis
Alzheimer Disease
Neuroepithelial Cells
Brain
Serum Amyloid A Protein
Membrane Fluidity
Cholinergic Neurons
Poisons
Transgenic Mice
Phospholipids
Cell Count
Cholesterol
Membranes

ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Aging
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

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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 A 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 GT1a, in the brain of transgenic mouse AD model. GQ1bα and GT1a 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.",
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