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Int. J. Mol. Sci. 2012, 13(6), 7303-7327; doi:10.3390/ijms13067303
Review

The Toxicity of Amyloid ß Oligomers

1
, 1,2
, 3,*  and 1,*
Received: 2 May 2012; in revised form: 1 June 2012 / Accepted: 8 June 2012 / Published: 13 June 2012
(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)
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Abstract: Abstract: In this review, we elucidate the mechanisms of Aβ oligomer toxicity which may contribute to Alzheimer’s disease (AD). In particular, we discuss on the interaction of Aβ oligomers with the membrane through the process of adsorption and insertion. Such interaction gives rises to phase transitions in the sub-structures of the Aβ peptide from α-helical to β-sheet structure. By means of a coarse-grained model, we exhibit the tendency of β-sheet structures to aggregate, thus providing further insights to the process of membrane induced aggregation. We show that the aggregated oligomer causes membrane invagination, which is a precursor to the formation of pore structures and ion channels. Other pathological progressions to AD due to Aβ oligomers are also covered, such as their interaction with the membrane receptors, and their direct versus indirect effects on oxidative stress and intraneuronal accumulation. We further illustrate that the molecule curcumin is a potential Aβ toxicity inhibitor as a β-sheet breaker by having a high propensity to interact with certain Aβ residues without binding to them. The comprehensive understanding gained from these current researches on the various toxicity mechanisms show promises in the provision of better therapeutics and treatment strategies in the near future.
Keywords: molecular dynamics simulation; Alzheimer’s disease; amyloid β peptide; amyloid β oligomer toxicity mechanism; curcumin
molecular dynamics simulation; Alzheimer’s disease; amyloid β peptide; amyloid β oligomer toxicity mechanism; curcumin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Zhao, L.N.; Long, H.W.; Mu, Y.; Chew, L.Y. The Toxicity of Amyloid ß Oligomers. Int. J. Mol. Sci. 2012, 13, 7303-7327.

AMA Style

Zhao LN, Long HW, Mu Y, Chew LY. The Toxicity of Amyloid ß Oligomers. International Journal of Molecular Sciences. 2012; 13(6):7303-7327.

Chicago/Turabian Style

Zhao, Li Na; Long, Hon Wai; Mu, Yuguang; Chew, Lock Yue. 2012. "The Toxicity of Amyloid ß Oligomers." Int. J. Mol. Sci. 13, no. 6: 7303-7327.



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