It’s sweet, it’s safe, and it looks like it could save neurons. What is it? Trehalose.
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.
Intestinal inflammation in mice can be dampened by giving them a diet restricted in amino acids, the building blocks of proteins, researchers have found. The results were published online by Nature on Wednesday, MarchÂ 16.
The findings highlight an ancient connection between nutrient availability and control of inflammation. They also suggest that a low protein diet — or drugs that mimic its effects on immune cells — could be tools for the treatment of inflammatory bowel diseases, such as Crohnâ€™s disease or ulcerative colitis.
The research team, led by Emory Vaccine Center immunologist Bali Pulendran, discovered that mice lacking the amino acid sensor GCN2 are more sensitive to the chemical irritant DSS (dextran sodium sulfate), often used to model colitis in animals. This line of research grew out of the discovery by Pulendran and colleagues that GCN2 is pivotal for induction of immunity to the yellow fever vaccine.
â€œIt is well known that the immune system can detect and respond to pathogens, but these results highlight its capacity to sense and adapt to environmental changes, such as nutritional starvation, which cause cellular stress,â€ he says.
Neale Weitzmann and George Beck have been publishing a series of papers describingÂ how silica nanoparticles can increase bone mineral density in animals. Their findings could someday form the basis for a treatment for osteoporosis.
In 2012, we posted an article and video on this topic. We wanted to call attention to a few of theÂ team’sÂ recent papers, one of which probes the mechanism for aÂ remarkable phenomenon: how can very fine silica particles stimulate bone formation?
The particlesâ€™ properties seem to depend on their size: 50 nanometers wide â€“ smaller than a HIV or influenza vision.Â In a 2014 ACS Nano paper, Beck, Weitzmann and postdoc Shin-Woo Ha show that the particles interact with particular proteins involved in the process of autophagy, a process of â€œself digestionâ€ induced by stress.
â€œThese studies suggest that it is not the material per se that stimulates autophagy but rather size or shape,â€ they write. Read more
The idea that particular lipid components, such as omega-3 fatty acids, promote health is quite familiar, so the finding that the lipid oleoylethanolamide or OEA extends longevity in the worm C. elegans is perhaps not so surprising. However, a recent paper in Science is remarkable for what it reveals about how OEA exerts its effects.
Scientists at Baylor College of Medicine led by Meng Wang, with some help from biochemists Eric Ortlund and Eric Armstrong at Emory, discovered that OEA is a way one part of the cell, the lysosome, talks to another part, the nucleus. Lysosomes are sort of recycling centers/trash digestersÂ (important for autophagy) and the nucleus is the control tower for the cell. The authors show that starting in lysosomes, OEA travels to the nucleus and activates nuclear hormone receptors (the Ortlund labâ€™s specialty). Read more
Researchers at Emory have been revealing several connections between cellsâ€™ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmedâ€™s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.
This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine. Read more
Update: Yoshinori Ohsumi’s 2016 Nobel Prize was for the study of autophagy. Hepatologist Mark Czaja, who came to Emory in 2015, is well known for his work on autophagy in the liver.
Feeling hungry? For this month’s Current Concept feature, lets take a look at the term autophagy. Taken literally, its Greek roots mean “self-digestion”.
Autophagy in mouse liver cells — the autophagic vesicles are green (Image from PNAS)
Autophagy is a basic response of cells to not having enough nutrients or other forms of stress: they begin to break down parts of the cell that are broken or not needed. The term autophagy was coined by Belgian biochemist Christian de Duve in the 1960s. He discovered lysosomes, the parts of the cell where breakdown can take place.
Autophagy comes up in many contexts in biomedical research. Indeed, there is an entire scientific journal devoted to the topic. At Emory, researchers interested in cancer, Parkinson’s, stroke and liver disease all have touched upon the process of autophagy. Read more