Neuronal membranes are key to the pathogenesis of Alzheimer's disease

the role of both raft and non-raft membrane domains

R. Williamson, C. Sutherland

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    Membrane rafts are sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts isolated from post-mortem AD brain are enriched in both ß-amyloid and phosphorylated tau. Proteolytic processing of APP to generate ß-amyloid, the principle component of amyloid plaques, can occur in membrane rafts, implicating them in the pathogenesis of Alzheimer's disease (AD). Secondary to their role in ß-amyloid generation, membrane rafts have more recently been implicated in the accumulation, aggregation and degradation of ß-amyloid, with evidence supporting a specific role for membrane raft gangliosides in the binding and aggregation of ß-amyloid. In addition, membrane domain composition has a direct impact on both the generation of ß-amyloid and its subsequent toxic actions and as such is a key target for the development of therapeutic strategies. This mini-review will focus on recent advances in our understanding of the relevance of membrane composition, of both raft and non-raft domains, to AD progression in models and in human disease. We will discuss how manipulation of membrane composition can alter both the proteolytic processing of APP and the subsequent binding and aggregation of ß-amyloid peptide. © 2011 Bentham Science Publishers Ltd.
    Original languageEnglish
    Pages (from-to)213-221
    Number of pages9
    JournalCurrent Alzheimer Research
    Volume8
    Issue number2
    Publication statusPublished - Mar 2011

    Keywords

    • Amyloid
    • cholesterol
    • lipid
    • membrane raft
    • AMYLOID PRECURSOR PROTEIN
    • TRANSGENIC MOUSE MODEL
    • GAMMA-SECRETASE ACTIVITY
    • DOCOSAHEXAENOIC ACID
    • BETA-PROTEIN
    • LIPID RAFTS
    • IN-VITRO
    • DEPENDENT MECHANISM
    • ENDOGENOUS SEED
    • CHOLESTEROL

    Cite this

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    title = "Neuronal membranes are key to the pathogenesis of Alzheimer's disease: the role of both raft and non-raft membrane domains",
    abstract = "Membrane rafts are sterol-and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts isolated from post-mortem AD brain are enriched in both {\ss}-amyloid and phosphorylated tau. Proteolytic processing of APP to generate {\ss}-amyloid, the principle component of amyloid plaques, can occur in membrane rafts, implicating them in the pathogenesis of Alzheimer's disease (AD). Secondary to their role in {\ss}-amyloid generation, membrane rafts have more recently been implicated in the accumulation, aggregation and degradation of {\ss}-amyloid, with evidence supporting a specific role for membrane raft gangliosides in the binding and aggregation of {\ss}-amyloid. In addition, membrane domain composition has a direct impact on both the generation of {\ss}-amyloid and its subsequent toxic actions and as such is a key target for the development of therapeutic strategies. This mini-review will focus on recent advances in our understanding of the relevance of membrane composition, of both raft and non-raft domains, to AD progression in models and in human disease. We will discuss how manipulation of membrane composition can alter both the proteolytic processing of APP and the subsequent binding and aggregation of {\ss}-amyloid peptide. {\circledC} 2011 Bentham Science Publishers Ltd.",
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    year = "2011",
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    language = "English",
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    Neuronal membranes are key to the pathogenesis of Alzheimer's disease : the role of both raft and non-raft membrane domains. / Williamson, R.; Sutherland, C.

    In: Current Alzheimer Research, Vol. 8, No. 2, 03.2011, p. 213-221.

    Research output: Contribution to journalArticle

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    AU - Sutherland, C.

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    KW - CHOLESTEROL

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