Naturally Occurring Protein Fragment in Brain Inhibits Key Enzyme implicated in Alzheimer’s disease

It could lead to the development of new drugs to treat the disease. The study found that the protein fragment, sAPPα, inhibits the proteolytic enzyme BACE1. Increased BACE1 activity contributes to production of the amyloid beta aggregates and plaques that are the hallmark of Alzheimer’s.

“Because sAPPα inhibits the BACE1 enzyme, it may be possible that it can be used to help prevent potentially dangerous increases in BACE1 activity, and thus prevent the onset of Alzheimer’s disease,” A/Prof Varghese John.

The protein fragment sAPPa is normally produced by neurons and is involved in maintenance of memory. John and his team employed a technique called small-angle X-ray scattering, or SAXS, and found that sAPPα inhibition of BACE1 activity is likely due to the unique, 3D structure of the protein fragment itself. Going forward, John and his team are determining the binding site of sAPPa to BACE1 using X-ray crystallography and other techniques.

“Our study suggests that developing sAPPα itself as a biologic, finding a smaller protein or peptide fragment that has similar effects, or identifying a chemical compound that increases levels of this beneficial protein fragment could be new and effective therapeutic strategies for mild cognitive impairment and Alzheimer’s patients,” John said. “These strategies could help normalize brain function and either restore memory and cognitive function, or prevent its decline.”

The protein fragment is critical to normal brain function, and creation of a new class of CNS therapeutics that enhances APPα may be of benefit beyond Alzheimer’s ie could help those with stroke, TBI, ALS http://www.newswise.com/articles/naturally-occurring-protein-fragment-found-in-the-brain-inhibits-key-enzyme-implicated-in-alzheimer-s-disease

Beta-secretase 1 (BACE1)… (Wikipedia) Alzheimer’s is the most common age-related dementia and the number of cases in the United States is expected to increase from the current number of about 5 to 6 million to 15 million by 2050. The costs to family life and on the health care system are enormous. Alzheimer’s and other dementias are projected to cost the United States $226 billion in 2015 alone, with that number rising to as high as $1.1 trillion in 2050.