Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Emory researchers see investigating 3q29 deletion as a way of unraveling schizophrenia’s biological and genetic Read more

B cells off the rails early in lupus

Emory scientists could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously Read more

Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

Keqiang Ye

Tangled up with tau

Pathologist Keqiang Ye and his colleagues have identified a new potential drug target in Alzheimer’s disease. It’s called SRPK2 (serine-arginine protein kinase 2).

Keqiang Ye, PhD

Depleting this enzyme from the brain using genetic engineering tools alleviates cognitive impairment in an animal model of Alzheimer’s. The result suggests that drugs Cheap Oakleys that target this enzyme could be valuable in the treatment of Alzheimer’s, although additional studies on human brain samples are necessary to fully confirm the findings, Ye says.

The results were published Tuesday in Journal of Neuroscience. The first author is postdoctoral fellow Yi Hong.

Hong and colleagues found that SRPK2 has elevated activity in a mouse model of Alzheimer’s. It acts on tau, one of the two major toxic clumpy proteins in Alzheimer’s. (beta-amyloid is outside the cell and forms plaques, tau is inside and forms tangles). Previous research on SRPK2 indicated that it had something to do with RNA splicing, so its “entanglement” with tau is a surprise.

Posted on by Quinn Eastman in Neuro Leave a comment

Dye me anticancer yellow

Over the last few years, pathologist Keqiang Ye and his colleagues have displayed an uncanny talent for finding potentially useful medicinal compounds. Recently another example of this talent appeared in Journal of Biological Chemistry.

Keqiang Ye, PhD

Postdoctoral fellow Qi Qi is first author on the paper. Collaborators include Jeffrey Olson, Liya Wang, Hui Mao, Haian Fu, Suresh Ramalingam and Shi-Yong Sun at Emory and Paul Mischel at UCLA.

Qi and Ye were looking for compounds that could inhibit the growth of an especially aggressive form of brain cancer, glioblastoma with deletion in the tumor suppressor gene PTEN. Tumors with this deletion do not respond to currently available targeted therapies.

The researchers found that acridine yellow G, a fluorescent dye used to stain microscope slides, can inhibit the growth of this tumor:

Oral administration of this compound evidently decreases the tumor volumes in both subcutaneous and intracranial models and elongates the life span of brain tumor inoculated nude mice. It also displays potent antitumor effect against human lung cancers. Moreover, it significantly decreases cell proliferation and enhances apoptosis in tumors…

Optimization of this compound by improving its potency through medicinal chemistry modification might warrant a novel anticancer drug for malignant human cancers.

Ye’s team observed that acridine yellow G appears not to be toxic in rodents. However, the acridine family of compounds tends to intercalate (insert itself) into DNA and can promote DNA damage, so more toxicology studies are needed. Other acridine family compounds such as quinacrine have been used to treat bacterial infections and as antiinflammatory agents, they note.

A paramecium stained with acridine orange, which shows anticancer activity for tumors containing PTEN mutations

Posted on by Quinn Eastman in Cancer Leave a comment

Drug discovery: shifting from brain growth factors to insulin

Earlier this year, the FDA put limitations on some anti-diabetic drugs because of their cardiovascular risks. The prevalence of diabetes in the United States continues to increase and is now above 8 percent of the population, so the need for effective therapies remains strong.

Keqiang Ye, PhD

Pathologist Keqiang Ye and colleagues have a paper in the Journal of Biological Chemistry describing their identification of a compound that mimics the action of insulin. This could be the starting point for developing new anti-diabetes drugs.

The new research is an extension of the Ye laboratory’s work on TrkA and TrkB, which are important for the response of neurons to growth factors. Ye and Sung-Wuk Jang, a remarkably productive postdoc who is now an assistant professor at Korea University, developed an assay that allowed them to screen drug libraries for compounds that directly activate TrkA and TrkB. This led them to find a family of growth-factor-mimicking compounds that could treat conditions such as Parkinson’s disease, depression and stroke.

Since TrkA/B and the insulin receptor are basically the same kind of molecule — receptor tyrosine kinases– and use some of the same cellular circuitry, Ye and Jang’s assay could also be used with the insulin receptor. Kunyan He and Chi-Bun Chan are the first two authors on the new paper. They report that the compound DDN can make cells more sensitive to insulin and improve their ability to take up glucose. They show that DDN (5,8-diacetyloxy-2,3-dichloro-1,4- naphthoquinone) can lower blood sugar, both in standard laboratory mice and in obese mice that serve as a model for type II diabetes.

Ye reports that he and his colleagues are working with medicinal chemists to identify related compounds that may have improved efficacy and potency.

“I hope in the near future we may have something that could replace insulin for treating diabetes orally,” he says.

Posted on by Quinn Eastman in Uncategorized Leave a comment

A new class of brain-protecting drugs

Pathologist Keqiang Ye has made a series of discoveries recently, arising from his investigations of substances that can mimic the growth factor BDNF (brain-derived neurotrophic factor).

BDNF is a protein produced by the brain that pushes neurons to withstand stress and make new connections. Some neuroscientists have described BDNF as “Miracle Gro for brain cells.”

“BDNF has been studied extensively for its ability to protect neurons vulnerable to degeneration in several diseases, such as ALS, Parkinson’s and Alzheimer’s disease,” Ye says. “The trouble with BDNF is one of delivery. It’s a protein, so it can’t cross the blood-brain barrier and degrades quickly.”

Working with Ye, postdoctoral fellow Sung-Wuk Jang identified a compound called 7,8-dihydroxyflavone that can duplicate BDNF’s effects on neurons and can protect them against damage in animal models of seizure, stroke and Parkinson’s disease. The compound’s selective effects suggest that it could be the founder of a new class of brain-protecting drugs. The results were published in Proceedings of the National Academy of Sciences.

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Posted on by Quinn Eastman in Neuro 1 Comment