Triple play in science communication

We are highlighting Emory BCDB graduate student Emma D’Agostino, who is a rare triple play in the realm of science communication. Emma has her own blog, where she talks about what it’s like to have cystic fibrosis. Recent posts have discussed the science of the disease and how she makes complicated treatment decisions together with her doctors. She’s an advisor to the Cystic Fibrosis Foundation on patient safety, communicating research and including the CF community Read more

Deep brain stimulation for narcolepsy: proof of concept in mouse model

Emory neurosurgeon Jon Willie and colleagues recently published a paper on deep brain stimulation in a mouse model of narcolepsy with cataplexy. Nobody has ever tried treating narcolepsy in humans with deep brain stimulation (DBS), and the approach is still at the “proof of concept” stage, Willie says. People with the “classic” type 1 form of narcolepsy have persistent daytime sleepiness and disrupted nighttime sleep, along with cataplexy (a loss of muscle tone in response Read more

In current vaccine research, adjuvants are no secret

Visionary immunologist Charlie Janeway was known for calling adjuvants – vaccine additives that enhance the immune response – a “dirty little secret.” Janeway’s point was that foreign antigens, by themselves, were unable to stimulate the components of the adaptive immune system (T and B cells) without signals from the innate immune system. Adjuvants facilitate that help. By now, adjuvants are hardly a secret, looking at some of the research that has been coming out of Emory Read more

delta-secretase

Amyloid vs tau? With this AD target, no need to choose

Keqiang Ye’s lab at Emory recently published a paper in Nature Communications that offers a two for one deal in Alzheimer’s drug discovery.

Periodically we hear suggestions that the amyloid hypothesis, the basis of much research on Alzheimer’s disease, is in trouble. Beta-amyloid is a toxic protein fragment that accumulates in extracellular brain plaques in Alzheimer’s, and genetics for early-onset Alzheimer’s point to a driver role for amyloid too.

In mice, inhibiting AEP hits two targets (amyloid and tau) with one shot

Unfortunately, anti-amyloid agents (either antibodies that sop up beta-amyloid or drugs that steer the body toward making less of it) have not shown clear positive effects in clinical trials.

That may be because the clinical trials started too late or the drugs weren’t dosed/delivered right, but there is a third possibility: modifying amyloid by itself is not enough.

Ye’s lab has been investigating an enzyme called AEP (asparagine endopeptidase), which he provocatively calls “delta secretase.” AEP is involved in processing both amyloid and tau, amyloid’s intracellular tangle-forming counterpart. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

The secrets of a new Alzheimer’s secretase

The title of Keqiang Ye’s recent Nature Communications paper contains a provocative name for an enzyme: delta-secretase.

Just from its name, one can tell that a secretase is involved in secreting something. In this case, that something is beta-amyloid, the toxic protein fragment that tends to accumulate in the brains of people with Alzheimer’s disease.

Aficionados of Alzheimer’s research may be familiar with other secretases. Gamma-secretase was the target of some once-promising drugs that failed in clinical trials, partly because they also inhibit Notch signaling, important for development and differentiation in several tissues. Now beta-secretase inhibitors are entering Alzheimer’s clinical trials, with similar concerns about side effects.

Many Alzheimer’s researchers have studied gamma- and beta-secretases, but a review of the literature reveals that so far, only Ye and his colleagues have used the term delta-secretase.

This enzyme previously was called AEP, for asparagine endopeptidase. AEP appears to increase activity in the brain with aging and cleaves APP (amyloid precursor protein) in a way that makes it easier for the real bad guy, beta-secretase, to produce bad beta-amyloid.*At Alzforum, Jessica Shugart describes the enzyme this way:

Like a doting mother, AEP cuts APP into bite-sized portions for toddler BACE1 [beta-secretase] to chew on, facilitating an increase in beta-amyloid production. Read more

Posted on by Quinn Eastman in Neuro Leave a comment