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The Toxicity of Amyloid ß Oligomers
School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637731, Singapore
High Performance Computing Centre, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore
* Authors to whom correspondence should be addressed.
Received: 2 May 2012; in revised form: 1 June 2012 / Accepted: 8 June 2012 / Published: 13 June 2012
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
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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.
Zhao LN, Long HW, Mu Y, Chew LY. The Toxicity of Amyloid ß Oligomers. International Journal of Molecular Sciences. 2012; 13(6):7303-7327.
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.