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Biological Targeting and Activity of Pre-fibrillar Aβ Assemblies

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Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases

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Abstract

The body of work from the past decade has advanced our understanding of how toxic oligomers of Aβ are capable of eliciting the spectrum of pathological and behavioral hallmarks of Alzheimer’s disease. These potent neurotoxins now provide a molecular basis for the cause of this disease as well as a basis for identifying and evaluating diagnostic and therapeutic strategies. Oligomer toxicity is mediated by a number of factors—both in the targeting of these toxins to the neuronal synapses and in the transduction of this targeting into intracellular signals resulting in synapse loss and, eventually, cell death. Recent investigations have focused on defining the mechanisms of binding of toxic Aβ oligomers, the pathways modulated by these events, and strategies to treat Alzheimer’s disease by targeting both aspects. One promising facet of recent research highlighted in this chapter, and in which Aβ oligomers play a central role, is the unfolding of connection between Alzheimer’s disease and insulin signaling in the aging brain.

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  1. Department of Neurobiology, Northwestern University, Evanston, IL, USA

    Kyle C. Wilcox, Jason Pitt, Adriano Sebollela, Helen Martirosova, Pascale N. Lacor & William L. Klein

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  1. Kyle C. Wilcox
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  2. Jason Pitt
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Correspondence to William L. Klein .

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  1. , Research School of Biology, Australian National University, Linnaeus Way, Canberra, 0200, Aust Capital Terr, Australia

    Farid Rahimi

  2. , Neurology, University of California at Los Angeles, Charles E. Young Drive South 635, Los Angeles, 90095-7334, California, USA

    Gal Bitan

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Wilcox, K.C., Pitt, J., Sebollela, A., Martirosova, H., Lacor, P.N., Klein, W.L. (2012). Biological Targeting and Activity of Pre-fibrillar Aβ Assemblies. In: Rahimi, F., Bitan, G. (eds) Non-fibrillar Amyloidogenic Protein Assemblies - Common Cytotoxins Underlying Degenerative Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2774-8_4

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