Detoxification Depot for β -Amyloid Peptides

Pazhani      Sundaram; Ranjini   K.   Sundaram; Chinnaswamy      Kasinathan; Stanley      Stein

doi:10.2174/156720508783884684

Abstract

Alzheimers Disease (AD) is caused by the deposition of insoluble and toxic amyloid peptides (Aβ) in the brain leading to memory loss and other associated neurodegenerative symptoms. To date there is limited treatment options and strategies for treating AD. Studies have shown that clearance of the amyloid plaques from the brain and thus from the blood could be effective in stopping and or delaying the progression of the disease. Small peptides derived from the Aβ- 42 sequence, in particular KLVFF, have shown to be effective binders of Aβ peptides and thus could be useful in delaying progression of the disease. We have taken advantage of this property by generating the retro-inverso (RI) version of this peptide, ffvlk, in different formats. We are presenting a new detox gel system using poly ethylene glycol (PEG), polymerized and cross linked with the RI peptides. We hypothesize that detox gel incorporating RI peptides will act like a ‘sink’ to capture the Aβ peptides from the surrounding environment. We tested these detox gels for their ability to capture biotinylated Aβ-42 peptides in vitro. The results showed that the detox gels bound Aβ-42 peptides effectively and irreversibly. Gels incorporating the tetramer RI peptide exhibited maximum binding capacity. The detox gel could be a potential candidate for treatment strategies to deplete the brain of toxic amyloid peptides.

Keywords: Alzheimer's disease, amyloid, Aβ, detox gels, RI peptides

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