By the end of 2014, Alzheimer’s disease (AD) will have cost the American society $214 billion dollars, affecting some 5.2 million Americans and resulting in 500,000 deaths this year. More importantly, AD is currently the only cause of death in the top 10 that cannot be treated, prevented, or have symptoms mitigated. AD is caused by the aggregation of the amyloid-beta protein (Aβ) that results in plaques accumulating between the neural cells in the brain. As time progresses, cellular death occurs, resulting in changes in personality and memory loss. Small molecules and peptides have been investigated to act as a preventative measure against AD, however, poor bioavailability and protease degradation has prevented these options from developing into a viable treatment. Poly-N-substituted glyicines (peptoids) may serve as a means to incorporate the function of peptides with the bioavailability of small molecules.  We have previously reported a peptoid sequence that exhibited a polyproline type-I like helical secondary structure that modulated Aβ40 aggregation in-vitro in a concentration dependent manner. As a result of our peptoid sequence, we were able to effectively reduce the total number of fibrillar β-sheet structured aggregates. To further support our findings, we have since investigated the morphology of Aβ40 in the presence and absence of our peptoid sequence as well as compared the efficacy of our peptoid to known small molecule inhibitors that have been reported to prevent the formation of oligomers and fibrils. Based on this study, we strongly believe our peptoid is modulating Aβ aggregation by a unique method which allows rapid progression through the oligomeric stage to the more stable, insoluble fibril stage. Fibrils are believed to serve as a natural defense mechanism to prevent the continued cellular exposure to the toxic oligomers.

Peptoids modulate Aβ aggregation and alter morphology of fibril species

249th National Meeting (2015)

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