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

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.

journal_name

Curr Alzheimer Res

authors

Penke B,Paragi G,Gera J,Berkecz R,Kovács Z,Crul T,VÍgh L

doi

10.2174/1567205015666180911151716

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1191-1212

issue

13

eissn

1567-2050

issn

1875-5828

pii

CAR-EPUB-92977

journal_volume

15

pub_type

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