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 beta-protein (Abeta). Abeta undergoes a conformational transition from random coil to ordered structure rich in beta-sheets, especially after addition of lipid vesicles containing GM1 ganglioside. In AD brain, a complex of GM1 and Abeta, termed "GAbeta," has been found to accumulate. In recent years, Abeta 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.
Highlights
Gangliosides are expressed in the outer leaflet of the plasma membrane of the cells of all vertebrates and are abundant in the nervous system
Because amyloid b-protein (Ab) generation and GM1 accumulation probably occur in early endosomes, the results provide further evidence that endosomes are intimately involved in the Ab-associated pathology of Alzheimer’s disease (AD) [79]
Because gangliosides are enriched in neuronal membranes and bind to b-amyloid and amyloid precursor protein (APP), they are probably involved in the conformational changes in these molecules that are a hallmark of the pathogenesis of AD
Summary
The pathology of AD is closely related to lipid metabolism [21]. During aging and neurodegeneration, the physicochemical properties of membranes are altered. It is of note that the APP/ PSEN1 bigenic mice have significantly impaired memory despite having no significant changes in major brain gangliosides, but the GD3S2/2 mice have normal memory in the presence of substantial redistribution of gangliosides This suggests that the ganglioside alterations per se are not directly responsible for the cognitive effects in this study, with the possible exception of the putative neutrophic effects of elevated GM1. Our preliminary results indicated that a cholinergic neuron-specific ganglioside (GQ1ba) is elevated in an AD model of transgenic mice (Ariga et al, unpublished results), which is consistent with this view These observations may reflect a specific change in ganglioside metabolism that is associated with neurodegenerative processes underlying AD and other forms of dementia
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
