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Hunting neuron killers in Alzheimer's and TBI
Date:11/9/2012

Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disordersconditions like Alzheimer's disease and traumatic brain injury. To better diagnose and treat these neurological conditions, scientists first need to better understand the underlying causes of neuronal death.

Enter Huaxi Xu, Ph.D., professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center. He and his team have been studying the protein appoptosin and its role in neurodegenerative disorders for the past several years. Appoptosin levels in the brain skyrocket in conditions like Alzheimer's and stroke, and especially following traumatic brain injury.

Appoptosin is known for its role in helping the body make heme, the molecule that carries iron in our blood (think "hemoglobin," which makes blood red). But what does heme have to do with dying brain cells? As Xu and his group explain in a paper they published October 31 in the Journal of Neuroscience, excess heme leads to the overproduction of reactive oxygen species, which include cell-damaging free radicals and peroxides, and triggers apoptosis, the carefully regulated process of cellular suicide. This means that more appoptosin and more heme cause neurons to die.

Not only did Xu and his team unravel this whole appoptosin-heme-neurodegeneration mechanism, but when they inhibited appoptosin in laboratory cell cultures, they noticed that the cells didn't die. This finding suggests that appoptosin might make an interesting new therapeutic target for neurodegenerative disorders.

What's next? Xu and colleagues are now probing appoptosin's function in mouse models. They're also looking for new therapies that target the protein.

"Since the upregulation of appoptosin is important for cell death in diseases such as Alzheimer's, we're now searching for small molecules that modulate appoptosin expression or activity. We'll then determine
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Contact: Heather Buschman
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert

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