Congratulations to Dr. Bess Frost on her new publication in Nature Neuroscience, “Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies.”

The Frost laboratory studies fundamental processes in cell biology that drive neurodegeneration and employs a multi-system approach to rapidly identify, test, and validate hypotheses.

The study, which was spearheaded by postdoctoral fellow Dr. Wenyan Sun, used fruit fly models to show that the toxic forms of tau that accumulate in neurodegenerative tauopathies causes active mobilization of transposable elements, and that transpososable element jumping causally contributes to death of neurons.

The researchers also showed that treating the fruit fly model with the drug lamivudine, a reverse transcriptase inhibitor that is approved for treating HIV and hepatitis B, could effectively halt transposable element jumping and reduce tau-induced neurotoxicity in the flies.

The team separately identified upregulated expression of transposable elements in postmortem brain tissue samples from patients with one of two different tauopathies, Alzheimer’s disease or progressive supranuclear palsy, implying that transposable element dysregulation may be at work in tau-related human neurodegenerative disorders.

“The toxic tau can be present, but if we give this drug and it blocks the transposable element activity, it’s enough to decrease the amount of brain cells that are dying in the fly model,” comments Dr. Frost, who is a member of the Barshop and Biggs Institutes at UT Health San Antonio. “We know that transposable elements are copying themselves at higher levels in the tauopathy fly model. And we know we can stop that from happening by giving them this drug.”The Frost laboratory studies fundamental processes in cell biology that drive neurodegeneration and employs a multi-system approach to rapidly identify, test, and validate hypotheses.

Their studies in fruit flies found that toxic tau protein deposition that is characteristic of tauopathies is associated with the disruption of epigenetic mechanisms that control the expression of transposable genetic elements, and that this dysregulation links with the death of neurons.

The researchers also showed that treating the fruit fly model using lamivudine, a reverse transcriptase inhibitor drug that is approved for treating HIV and hepatitis B, could effectively halt transposable element dysregulation and reduce tau-induced neurotoxicity in the flies.

The team separately identified upregulated expression of transposable elements in postmortem brain tissue samples from patients with two types of tauopathy, implying that similar mechanisms may be at work in some human neurodegenerative disorders.

“The toxic tau can be present, but if we give this drug and it blocks the transposable element activity, it’s enough to decrease the amount of brain cells that are dying in the fly model,” comments Dr. Frost, who is a member of the Barshop and Biggs Institutes at UT Health San Antonio. “We know that these genes are copying themselves at higher levels in the tauopathy fly model. And we know we can stop that from happening by giving them this drug.”