Xiao-Jiang Li: Focusing on the Pathogenesis of Huntington's Disease
Fast Breaking Paper Commentary, December 2010
Article: Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms
Authors: Bradford, J;Shin, JY;Roberts, M;Wang, CE;Li,
XJ;Li, S |
Xiao-Jiang Li talks with ScienceWatch.com and answers a few questions about this month's Fast Breaking Paper paper in the field of Neuroscience & Behavior.
Why do you think your paper is highly cited?
The paper presents strong evidence that expression of Huntington disease protein only in glial cells can also induce neurological symptoms in mice, indicating a critical role of glial function in neurodegenerative diseases.
Does it describe a new discovery, methodology, or synthesis of knowledge?
Yes, it describes a new Huntington disease mouse model and in vivo evidence for the effect of Huntington disease protein on glial function.
Would you summarize the significance of your paper in layman's terms?
Although Huntington disease is characterized by selective neurodegeneration in the brain, the role of non-neuronal cells, such as glial cells, in the disease remains unclear. Our study demonstrates that dysfunction of glial cells also contributes to the disease progression, providing a novel therapeutic target for Huntington disease.
How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?
I have been working on Huntington disease since the identification of the gene mutation for this disease in 1993. Although we know that this mutation causes protein misfolding and aggregation, we are unclear how the disease protein selectively kills neurons in an age-dependent manner. Understanding this issue should greatly help us to find effective therapeutic strategies.
Where do you see your research leading in the future?
We are focusing on the pathogenesis of Huntington disease by investigating different animal models. Comparing these models will provide important insight into the mechanisms by which the mutant protein selectively kills neurons in the brain.
Do you foresee any social or political implications for your research?
Our research aims to elucidate the mechanism of Huntington disease, which should have broad implications for understanding other age-dependent neurodegenerative diseases that are also caused by misfolded proteins in the brain.
Xiao-Jiang Li, M.D., Ph.D.
Distinguished Professor of Human Genetics
Department of Human Genetics
Emory University School of Medicine
Atlanta, GA, USA
KEYWORDS: EXCITOTOXICITY; GLIA; NEURODEGENERATION; POLYGLUTAMINE; GLUTAMATE; GLUTAMATE TRANSPORT; NEURODEGENERATIVE DISEASE; INTRANUCLEAR INCLUSIONS; TRANSGENIC MICE; GLIAL-CELLS; NEURONS; EXCITOTOXICITY; ACCUMULATION; PATHOGENESIS.