Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis

Vijayaraghavan Rangachari, Dexter N. Dean, Pratip Rana, Ashuwin Vaidya, Preetam Ghosh

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction. The aggregation process is highly stochastic involving both homotypic (Aβ-Aβ) and heterotypic (Aβ with interacting partners) interactions. Two of the important members of interacting partners are membrane lipids and surfactants, to which Aβ shows a perpetual association. Aβ–membrane interactions have been widely investigated for more than two decades, and this research has provided a wealth of information. Although this has greatly enriched our understanding, the objective of this review is to consolidate the information from the literature that collectively showcases the unique phenomenon of lipid-mediated Aβ oligomer generation, which has largely remained inconspicuous. This is especially important because Aβ aggregate “strains” are increasingly becoming relevant in light of the correlations between the structure of aggregates and AD phenotypes. Here, we will focus on aspects of Aβ-lipid interactions specifically from the context of how lipid modulation generates a wide variety of biophysically and biochemically distinct oligomer sub-types. This, we believe, will refocus our thinking on the influence of lipids and open new approaches in delineating the mechanisms of AD pathogenesis. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.

Original languageEnglish
Pages (from-to)1652-1662
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1860
Issue number9
DOIs
StatePublished - 1 Sep 2018

Fingerprint

Alzheimer Disease
Lipids
Oligomers
Agglomeration
Molecular Weight
Protein Conformation
Molecular weight
Poisons
Amyloid Plaques
Membrane Lipids
Amyloid
Surface-Active Agents
Cell membranes
Cell Membrane
Conformations
Brain
Phenotype
Peptides
Modulation
Association reactions

Keywords

  • Aggregation
  • Amyloid-beta
  • Lipids
  • Membrane
  • Oligomer
  • Strain
  • Surfactant

Cite this

Rangachari, Vijayaraghavan ; Dean, Dexter N. ; Rana, Pratip ; Vaidya, Ashuwin ; Ghosh, Preetam. / Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis. In: Biochimica et Biophysica Acta - Biomembranes. 2018 ; Vol. 1860, No. 9. pp. 1652-1662.
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Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis. / Rangachari, Vijayaraghavan; Dean, Dexter N.; Rana, Pratip; Vaidya, Ashuwin; Ghosh, Preetam.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1860, No. 9, 01.09.2018, p. 1652-1662.

Research output: Contribution to journalReview article

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