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The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View

[ Vol. 15 , Issue. 13 ]

Author(s):

Botond Penke*, Gábor Paragi, János Gera, Róbert Berkecz, Zsolt Kovács, Tim Crul and László VÍgh   Pages 1191 - 1212 ( 22 )

Abstract:


Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer’s disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the “calpain-cathepsin hypothesis” of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.

Keywords:

Lipids, membranes, Alzheimer's disease, lipids in Aβ aggregation, lipid-protein interactions, 4-hydroxy-2- nonenal, ApoE, membrane lipid therapy, lipid dietary factors.

Affiliation:

Department of Medical Chemistry, University of Szeged, Dom square 8, Szeged H-6720, Department of Medical Chemistry, University of Szeged, Dom square 8, Szeged H-6720, Department of Medical Chemistry, University of Szeged, Dom square 8, Szeged H-6720, Department of Medical Chemistry, University of Szeged, Dom square 8, Szeged H-6720, Savaria Department of Biology, Savaria University Centre, ELTE Eotvos Lorand University, H-9700 Szombathely, Karolyi Gáspar square 4, Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62, H-6726 Szeged, Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62, H-6726 Szeged



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