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Review
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Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers

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Review

Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers

Fátima Mesa-Herrera et al. Int J Mol Sci.

Abstract

Lipids in the brain are major components playing structural functions as well as physiological roles in nerve cells, such as neural communication, neurogenesis, synaptic transmission, signal transduction, membrane compartmentalization, and regulation of gene expression. Determination of brain lipid composition may provide not only essential information about normal brain functioning, but also about changes with aging and diseases. Indeed, deregulations of specific lipid classes and lipid homeostasis have been demonstrated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, recent studies have shown that membrane microdomains, named lipid rafts, may change their composition in correlation with neuronal impairment. Lipid rafts are key factors for signaling processes for cellular responses. Lipid alteration in these signaling platforms may correlate with abnormal protein distribution and aggregation, toxic cell signaling, and other neuropathological events related with these diseases. This review highlights the manner lipid changes in lipid rafts may participate in the modulation of neuropathological events related to AD and PD. Understanding and characterizing these changes may contribute to the development of novel and specific diagnostic and prognostic biomarkers in routinely clinical practice.

Keywords: Alzheimer’s disease; Parkinson disease.; biomarkers; lipid rafts; lipids; neurodegenerative diseases.

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic representation of amyloid precursor protein (APP) palmitoylation modulating both APP processing and Aβ generation in lipid rafts. (A). No APP palmitoylation. BACE1 (red) in lipid rafts cleaves APP at the β-cleavage site. Subsequent γ-secretase-mediated cleavage (γ) generates Aβ (orange). (B). APP palmitoylation. APP is palmitoylated, exhibiting a palmitic moiety (orange) attached to APP (pal-APP) that is recruited to lipid rafts. Our data suggest that palmitoylation may enhance BACE1-mediated cleavage of APP that may ultimately enhance generation of Aβ fragments and oligomerization. This and all the following figures were created with BioRender.com
Figure 2
Figure 2
Schematic summary of lipid raft alterations in Alzheimer’s Disease (AD). In this pathologic state, both monounsaturated oleic acid (18:1) and polyunsaturated docosahexaenoic acid (DHA, (n-3 PUFA)) are depleted. Moreover, three member of the sphingolipids family are also reduced: gangliosides, cerebrosides, and sulfatides.
Figure 3
Figure 3
Schematic summary of lipid raft alterations in Parkinson’s Disease (PD). In this pathologic state, polyunsaturated docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are depleted, while levels of saturated fatty stearic and palmitic acids are increased. Furthermore, lipid raft content in gangliosides and phosphatidylserine (PS) is also pathologically augmented.

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