Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis

@article{Kayed2003CommonSO,
  title={Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis},
  author={Rakez Kayed and Elizabeth Head and Jennifer Lynn Thompson and Theresa M. McIntire and Saskia Charlotte Florence Milton and Carl Cotman and Charles G Glabe},
  journal={Science},
  year={2003},
  volume={300},
  pages={486 - 489}
}
Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like the Aβ peptide in Alzheimer's disease (AD). Here we show that all of the soluble oligomers tested display a common conformation-dependent structure that is unique to soluble oligomers regardless of sequence. The in vitro toxicity of soluble oligomers is inhibited by oligomer-specific antibody. Soluble oligomers have a unique distribution in human AD brain that is distinct from fibrillar… 
Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis
TLDR
Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloids-associated degenerative disease, such as sporadic inclusion-body myositis.
Amyloid Oligomer Structures and Toxicity
TLDR
Focus on three common mechanisms of toxicity provides a means of simplifying the list of primary disease mechanisms and opens the possibility of developing broad spectrum therapeutics that target several amyloid related degenerative diseases.
Amyloid accumulation and pathogensis of Alzheimer's disease: significance of monomeric, oligomeric and fibrillar Abeta.
  • C. Glabe
  • Biology
    Sub-cellular biochemistry
  • 2005
This chapter reviews recent findings that indicate that soluble amyloid oligomers may represent the primary pathological species in Alzheimer's and other degenerative diseases. Various amyloids share
Molecular mechanisms of amyloid oligomers toxicity.
TLDR
It is suggested that the complexity and dynamic nature of amyloid oligomers may be responsible for the discrepancy among these mechanisms and the proposed cellular targets for amyloids oligomers.
Common mechanisms of amyloid oligomer pathogenesis in degenerative disease
  • C. Glabe
  • Biology
    Neurobiology of Aging
  • 2006
Structural Classification of Toxic Amyloid Oligomers*
  • C. Glabe
  • Biology
    Journal of Biological Chemistry
  • 2008
TLDR
Conformation-dependent antibodies that recognize generic epitopes that are specifically associated with distinct aggregation states of many different amyloid-forming sequences indicate that there are at least two fundamentally distinct types of amyloidal oligomers: fibrillar and prefibrilar oligomers.
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