Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - A review

Toshio Ariga, Michael P. McDonald, Robert K Yu

Research output: Contribution to journalReview article

224 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1157-1175
Number of pages19
JournalJournal of Lipid Research
Volume49
Issue number6
DOIs
StatePublished - Jun 1 2008

Fingerprint

Gangliosides
Metabolism
Alzheimer Disease
Amyloid Plaques
G(M1) Ganglioside
Lipids
Serum Amyloid A Protein
Brain
Memory Disorders
Parkinsonian Disorders
Brain Diseases
Neurodegenerative diseases
Plasma Cells
Neurodegenerative Diseases
Cognition
Nervous System
Dementia
Vertebrates
Neurology
Pathology

Keywords

  • Amyloid β-protein
  • Lipid raft
  • Microdomain

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - A review. / Ariga, Toshio; McDonald, Michael P.; Yu, Robert K.

In: Journal of Lipid Research, Vol. 49, No. 6, 01.06.2008, p. 1157-1175.

Research output: Contribution to journalReview article

Ariga, Toshio ; McDonald, Michael P. ; Yu, Robert K. / Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease - A review. In: Journal of Lipid Research. 2008 ; Vol. 49, No. 6. pp. 1157-1175.
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