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Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
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In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
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Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
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Lipids function as structural components of cellular membranes, in addition to acting as energy reservoirs and signaling molecules. They are thus crucial to all living organisms.  The three biologically important classes of lipids are triglycerides, phospholipids, and steroids.
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Author Spotlight: Advancing Cell Membrane Biophysics - Exploring Interactions and Challenges Through Experimental and Computational Approaches
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APP Function and Lipids: A Bidirectional Link.

Marcus O W Grimm1, Janine Mett2, Heike S Grimm2

  • 1Experimental Neurology, Saarland UniversityHomburg/Saar, Germany; Neurodegeneration and Neurobiology, Saarland UniversityHomburg/Saar, Germany; Deutsches Institut für DemenzPrävention (DIDP), Saarland UniversityHomburg/Saar, Germany.

Frontiers in Molecular Neuroscience
|March 28, 2017
PubMed
Summary

Alzheimer's disease (AD) involves amyloid-beta (Aβ) plaques and altered brain lipids. This review explores the complex, two-way relationship between lipids, Aβ generation, and lipid metabolism in AD.

Keywords:
AICDAPP processingAbeta cholesterolPUFAgangliosideslipidssphingolipidssulfatides

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques, a major hallmark.
  • Lipids, particularly apolipoprotein E (ApoE) ε4, are significant risk factors for AD.
  • Altered lipid profiles in AD brains suggest lipids influence Aβ generation.

Purpose of the Study:

  • To review the bidirectional relationship between lipids and Alzheimer's disease.
  • To examine how lipids affect amyloid precursor protein (APP) processing and Aβ production.
  • To discuss the role of Aβ and AICD in regulating lipid homeostasis.

Main Methods:

  • Literature review of studies on lipids, AD, and APP processing.
  • Analysis of post-mortem brain lipid alterations in AD.
  • Investigation of lipids modulating APP secretase activity.
  • Examination of Aβ and AICD roles in lipid metabolism.

Main Results:

  • Lipid changes in AD brains are both a consequence and modulator of Aβ generation.
  • Specific lipids can decrease Aβ production, while others may exacerbate AD pathology.
  • APP processing enzymes and APP itself are transmembrane proteins, highlighting lipid impact.
  • Aβ and AICD influence lipid homeostasis through direct effects or gene regulation.

Conclusions:

  • A complex, bidirectional link exists between lipids and Alzheimer's disease.
  • Lipids critically impact Aβ generation by influencing APP processing.
  • Aβ and AICD play roles in regulating lipid metabolism pathways, affecting overall homeostasis.