β-amyloid inhibits protein prenylation and induces cholesterol sequestration by impairing SREBP-2 cleavage.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Amany MohamedElena Posse de Chaves

Abstract

Accumulation of β-amyloid (Aβ) inside brain neurons is an early and crucial event in Alzheimer's disease (AD). Studies in brains of AD patients and mice models of AD suggested that cholesterol homeostasis is altered in neurons that accumulate Aβ. Here we directly investigated the role of intracellular oligomeric Aβ(42) (oAβ(42)) in neuronal cholesterol homeostasis. We report that oAβ(42) induces cholesterol sequestration without increasing cellular cholesterol mass. Several features of AD, such as endosomal abnormalities, brain accumulation of Aβ and neurofibrillary tangles, and influence of apolipoprotein E genotype, are also present in Niemann-Pick type C, a disease characterized by impairment of intracellular cholesterol trafficking. These common features and data presented here suggest that a pathological mechanism involving abnormal cholesterol trafficking could take place in AD. Cholesterol sequestration in Aβ-treated neurons results from impairment of intracellular cholesterol trafficking secondary to inhibition of protein prenylation. oAβ(42) reduces sterol regulatory element-binding protein-2 (SREBP-2) cleavage, causing decrease of protein prenylation. Inhibition of protein prenylation represents a mechanism of oAβ(42)...Continue Reading

Citations

Jul 9, 2013·Experimental Cell Research·Jonathan DeGeer, Nathalie Lamarche-Vane
Oct 11, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marco SegattoValentina Pallottini
Apr 5, 2013·EMBO Molecular Medicine·Nathalie PierrotJean-Noël Octave
Jan 7, 2014·Molecular Neurobiology·David A Hottman, Ling Li
Nov 27, 2014·Journal of Bioenergetics and Biomembranes·Laura A MartinBarbara Karten
Dec 23, 2015·International Journal of Molecular Sciences·Ian James Martins
Dec 18, 2013·Journal of Neurochemistry·W Gibson WoodGunter P Eckert
Nov 11, 2017·Journal of Lipid Research·Amany MohamedElena Posse de Chaves
Oct 25, 2013·Protein Science : a Publication of the Protein Society·Yuanli SongCharles R Sanders
Nov 20, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei WangElina Ikonen
Sep 14, 2014·The Journal of Biological Chemistry·Leon M TaiMary Jo LaDu
Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kai YangTaolei Sun
Jan 9, 2021·Cell Death & Disease·Natalia P AlzaGabriela A Salvador
Nov 24, 2021·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Manale NounImane Abbas

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