Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this Read more

Mother's milk is OK, even for the in-between babies

“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them. “A nurse called to ask how my son was doing,” says Caspary, a developmental Read more

Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

progranulin

Granulins treasure not trash – potential FTD treatment strategy

Emory University School of Medicine researchers have developed tools that enable them to detect small proteins called granulins for the first time inside cells. Granulins are of interest to neuroscientists because mutations in the granulin gene cause frontotemporal dementia (FTD). However, the functions of granulins were previously unclear.

FTD is an incurable neurodegenerative disease and the most common type of dementia in people younger than 60. Genetic variants in the granulin gene are also a risk factor for Alzheimer’s disease and Parkinson’s disease, suggesting this discovery may have therapeutic potential for a broad spectrum of age-related neurodegenerative diseases.

The results were published August 9 by the journal eNeuro (open access).

Thomas Kukar, PhD

Some neuroscientists believed that granulins were made outside cells, and even could be toxic under certain conditions. But with the newly identified tools, the Emory researchers can now see granulins inside cells within lysosomes, which are critical garbage disposal and recycling centers. The researchers now propose that granulins have important jobs in the lysosome that are necessary to maintain brain health, suppress neuroinflammation, and prevent neurodegeneration.

Problems with lysosomes appear in several neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

“A lysosomal function for granulins is exciting and novel.  We believe it may provide an explanation why decreased levels of granulins are linked to multiple neurodegenerative diseases, ranging from frontotemporal dementia to Alzheimer’s,” says senior author Thomas Kukar, PhD, assistant professor of pharmacology and neurology and the Emory University Center for Neurodegenerative Disease. Read more

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A sweet brain preserver: trehalose

It’s sweet, it’s safe, and it looks like it could save neurons. What is it? Trehalose.

Trehalose molecule

Trehalose is a natural sugar.

This natural sugar is used in the food industry as a preservative and flavor enhancer (it’s in Taco Bell’s meat filling). And curiously, medical researchers keep running into trehalose when they’re looking for ways to fight neurodegenerative diseases.

A recent example from Emory’s Department of Pharmacology: Chris Holler, Thomas Kukar and colleagues were looking for drugs that might boost human cells’ production of progranulin (PGRN), a growth factor that keeps neurons healthy. Mutations in the progranulin gene are a common cause of frontotemporal dementia.

The Emory scientists discovered two leads: a class of compounds called mTOR inhibitors — the transplant drug rapamycin is one — and trehalose. The team decided to concentrate on trehalose because it increased PGRN levels in neuronal and non-neuronal cell types, unlike the mTOR inhibitors. Their results were published at the end of June in Molecular Neurodegeneration.

The team confirmed their findings by examining the effects of trehalose on cells derived from patients with progranulin mutations. This paper is the first to include results from Emory’s Laboratory of Translational Cell Biology, which was established in 2012 to facilitate this type of “disease in a dish” approach. Cell biologists Charles Easley, Wilfried Rossoll and Gary Bassell from the LTCB, and neurologists Chad Hales and William Hu from the Center for Neurodegenerative Disease are co-authors.

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Posted on by Quinn Eastman in Neuro 1 Comment