The U.S. Defense Advanced Research Projects Agency (DARPA) has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections. The award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation, and clinical medicine. The team includes Sanford-Burnham’s Erkki Ruoslahti, M.D., Ph.D., and is led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego. Also on the team are Sangeeta N. Bhatia, M.D., Ph.D., of Massachusetts Institute of Technology, and Clark C. Chen, M.D., Ph.D., of UC San Diego School of Medicine.
These nanoparticles of porous silicon, each 100 times smaller than a human hair, contain microscopic reservoirs that can hold and protect sensitive drugs. The surface of the particles can be covered with targeting molecules. (Photo by Chia-Chen Wu, UC San Diego)
In Alzheimer's and traumatic brain injury, neurons (red) are killed off by the protein appoptosin
Sanford-Burnham researchers discovered that the protein appoptosin prompts neurons to commit suicide in several neurological conditions—giving them a new therapeutic target for Alzheimer’s disease and traumatic brain injury.
Dying neurons lead to cognitive impairment and memory loss in patients with neurodegenerative disorders–conditions 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 Center for Neuroscience, Aging, and Stem Cell Research. 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 recently 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.