Protein Shapes Matter in Alzheimer's Research

A study from Michigan Technological University (MTU) published in ACS Chemical Neuroscience found that the cumulative effect of misfolded proteins can lead to neurodegenerative diseases like Alzheimer's, reports ScienceDaily . For amyloid beta peptides, a common chemical alteration at a particular molecular site — acetylation — causes a chain reaction that leads to protein misfolding, accrual, and cellular toxicity. Acetylation can occur at two locations on amyloid beta proteins: lysine 16 and lysine 28. The lysine 16 acetylation occurrence leads to the disordered aggregates that form sticky but flexible structures with high toxicity levels, and which also exhibit higher free radical formation. "The shape, stickiness, and flexibility of the aggregated protein structure can play a vital role in the cellular toxicity and may also affect the mechanism of toxicity," said MTU Professor Ashutosh Tiwari. In Alzheimer's, these aggregates build up in the region of the brain that affects memory. "This is how a subtle change on a single position can affect a whole protein's aggregation," Tiwari noted.