title: The toxicity of amyloid β oligomers.
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.
authors: School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637731, Singapore.
authors: Li Na
authors: LN
authors: Zhao
authors: 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.
authors: Hon Wai
authors: HW
authors: Long
authors: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore.
authors: Yuguang
authors: 0000-0002-2499-026X
authors: Y
authors: Mu
authors: School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637731, Singapore.
authors: Lock Yue
authors: 0000-0003-1366-8205
authors: LY
authors: Chew
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin