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Reviews

Small-molecule inhibitors/modulators of amyloid-β peptide aggregation and toxicity for the treatment of Alzheimer's disease: a patent review (2010 – 2012)

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Pages 581-596 | Published online: 21 Feb 2013
 

Abstract

Introduction: Genetic, physiological, and biochemical data indicate that agglomerates of the 42-amino acid form of the amyloid-β (Aβ42) peptide are strongly linked to Alzheimer's disease (AD) etiology and thus represent a particularly attractive target for the development of an effective disease-modifying approach for AD treatment. A plethora of chemical entities able to modulate Aβ42 self-assembly have been developed in recent years, among them, several are in clinical or preclinical development.

Areas covered: This review accounts for small-molecule inhibitors of Aβ peptide polymerization and toxicity, reported in the patent literature during the 2010 – 2012 period, and their potential use as disease-modifying therapeutics for AD cure.

Expert opinion: The earliest pathogenic event is the formation of soluble Aβ oligomers that disrupt synaptic communication. Drug design strategies targeting these primary toxic agents could hold considerable promises for obtaining effective anti-AD drugs candidate. The heterogeneous aggregation of Aβ and the resulting difficulty to structurally characterize the peptide represent important drawbacks.

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