Compartmentalization of β-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts

@article{Riddell2001CompartmentalizationO,
  title={Compartmentalization of $\beta$-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts},
  author={David R. Riddell and Gary Christie and Ishrut Hussain and Colin Dingwall},
  journal={Current Biology},
  year={2001},
  volume={11},
  pages={1288-1293}
}
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321 Citations
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321 Citations

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The association of all four components of the γ-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts is described.
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Recent research developments that shed light on the association of  -secretase and � -secret enzyme with lipid rafts are summarized and discussed, and their implications for the pathology and therapeutics of AD are discussed.
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The results suggest that not only the cellular level of cholesterol but also that of sphingolipids may be involved in the pathological process of Alzheimer's disease by modulating APP cleavage.
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TLDR
This mini-review focuses on the roles of lipid rafts in the biogenesis and catabolism of Aβ, covering recent research on the relationship between cholesterol-rich membrane microdomains and the three secretases or Aβ-degrading peptidases.
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It is found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the absence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α- secretase activity.
Alzheimer Disease Aβ Production in the Absence of S-Palmitoylation-dependent Targeting of BACE1 to Lipid Rafts*
TLDR
It is demonstrated that Bace1 undergoes S-palmitoylation at four Cys residues at the junction of transmembrane and cytosolic domains, and Ala substitution at these four residues is sufficient to displace BACE1 from lipid rafts.
β-secretase processing of the Alzheimer’s amyloid protein precursor (APP)
TLDR
It is argued that BACE is not limiting for Aβ production and the existence of a high molecular weight complex of BACE that is more active than the monomer is reported, and evidence that the BACE complex is enriched in lipid raft fractions prepared from brain membranes is presented.
Association of active γ-secretase complex with lipid rafts Published, JLR Papers in Press, Feburary 16, 2005. DOI 10.1194/jlr.M400333-JLR200
TLDR
Results suggest that both cholesterol and protein isoprenylation influence the active γ-secretase complex association with lipid rafts in human neuroblastoma cells.
The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein.
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