Browse by Medical Category
Find a Researcher
View the MIND website
Research Investigator Profile
Antonio Valencia, PhD
My research focuses on the molecular mechanisms of neurodegeneration in Huntington’s disease (HD), including oxidative stress, signaling pathways, cellular membranes, and cell death. The main model for my studies is a homozygous HD mouse model expressing mutant huntingtin (140-Q repeats), which causes HD. I have demonstrated that primary HD neurons die more rapidly than control neurons, which is prevented by blocking the early increase of reactive oxygen species (ROS). I identified the source of ROS in HD, the NADPH oxidase or NOX2, which generates superoxide inducing an elevation of ROS. NOX activity is higher in HD neurons and brain tissue than controls, however the mechanism of activation is unknown and still under investigation. Interestingly, pre-symptomatic HD human brains have higher levels of NOX activity than advanced HD brains. Furthermore, oxidation of synaptic proteins occurs in HD mouse brains. Currently, I am studying a crossbreed mouse model HD/NOX- (Q140 HD with a NOX2 knockout). Using HD/NOX2- mice shows that NOX2 activation induces ROS increase and neurodegeneration in HD. NOX2 activation occurs in lipid rafts, therefore my interest on studying these micro-domains in HD. There are deficits in lipid rafts components in HD, including neurons, mouse and human brain. Now, I am designing experiments directed to treat HD mice with small molecules and follow up using behavior tests and biochemical markers. My goal is to find potential targets that can be helpful to find a therapy for HD.
View poster: Early Increase in the NADPH-Oxidase (NOX2) Activity Contributes to Oxidative Stress and Neurodegeneration in Huntington's Disease - PDF
Learn more about the Laboratory of Cellular Neurobiology.
MassGeneral Institute for Neurodegenerative Disease (MIND)114 16th St, Room 2125HCharlestown MA, 02129
Back to Top