Lipid rafts: Keys to neurodegeneration

The increase in life expectancy seen in many countries has been accompanied by an increase in the number of people living with dementia and a growing need for health care. The large number of affected individuals emphasizes the need to identify causes for the phenotypes associated with diseases such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, Huntington's, and those caused by prions. This review addresses the hypothesis that changes in lipid rafts induced by alterations in their ganglioside and/or cholesterol content or the interaction of mutant proteins with them provide the keys to understanding the onset of neurodegeneration that can lead to dementia. The biological function(s) of raft-associated gangliosides and cholesterol are discussed prior to reviewing what is known about their roles in lipid rafts in the aforementioned diseases. It concludes with some questions that need to be addressed in order to provide investigators with the basis for identifying small molecule agonists or antagonists to test as potential therapeutics. (C) 2010 Elsevier Inc. All rights reserved.