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neurofibrillary tangles

Acidity of aging leads to new Alzheimer’s drug target

Pathologist Keqiang Ye and his colleagues have been studying the functions of an enzyme called AEP, or asparagine endopeptidase, in the brain. AEP is activated by acidic conditions, such as those induced by stroke or seizure.

AEP is a protease. That means it acts as a pair of scissors, snipping pieces off other proteins. In 2008, his laboratory published a paper in Molecular Cell describing how AEP’s acid-activated snipping can unleash other enzymes that break down brain cells’ DNA.

Following a hunch that AEP might be involved in neurodegenerative diseases, Ye’s team has discovered that AEP also acts on tau, which forms neurofibrillary tangles in Alzheimer’s disease.

“We were looking for additional substrates for AEP,” Ye says. “We knew it was activated by acidosis. And we had read in the literature that the aging brain tends to be more acidic, especially in Alzheimer’s.”

The findings, published in Nature Medicine in October, point to AEP as a potential target for drugs that could slow the advance of Alzheimer’s, and may also lead to improved diagnostic tools. Read more

Posted on by Quinn Eastman in Neuro Leave a comment