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

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

GM1 Ganglioside Inhibits β‐Amyloid Oligomerization Induced by Sphingomyelin

“…Our findings suggest that decreasing GM 1 levels (reported to occur with age)7, 8a, 19 could lead to reduced protection from the oligomerization‐triggering effect of Sph and thus contribute to spark AD's onset. The provided molecular insights support reports on the neuroprotective effects of GM 1 in cell cultures and rat models of AD 9, 20.…”

“…Importantly, ganglioside concentration in the brain decreases with AD development, and GM 1 is known to have neuroprotective and neurorestorative effects 8. Recent reports state that GM 1 can reduce toxicity induced by Aβ peptides in vivo 8a, 9…”

High Levels of Anti-Ganglioside Antibodies in Patients with Parkinson?s Disease Associated with Cognitive Decline

“…Exogenous GM1 treatment has been used to treat symptoms of Parkinson's disease, though both in human and animal models. Based on these studies, GM1 protects against nigrostriatal toxicity and associated motor symptoms induced by 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine in mice and monkeys [72][73][74][75][76]. GM1 treatment restored cognitive and motor function and prevented decline in function in a 90 week trial in monkeys.…”

How Does N- and O-Glycosylation Affect the Formation and Accumulation of Amyloid β-Peptide?

“…In the AD brain, a complex of GM1 ganglioside and Aβ has been found to accumulate (50). Recent reports showed that ganglioside interactions with Aβ in the endocytic compartments seem to mediate Aβ accumulation in the brain (50,51), although the precise mechanism remains to be clarified. Immune activation is considered to affect neurodegeneration as a double-edged sword, and therefore proper activation of microglia is necessary for Aβ clearance.…”