The goal of this research unit is to understand the molecular mechanisms leading to neuronal (brain cell) death in Huntington Disease, an incurable genetic disorder that usually strikes in mid-life, causing progressive, irreversible and ultimately fatal neurological damage. With a focus on the fundamental molecular structure and function of neurons, such research also has relevance in understanding the development and effects of other degenerative neurological disorders, such as Alzheimer’s and Parkinson’s Disease, and for understanding recovery from brain injury. As the study of disease reveals information about normal structure and function, this research will also contribute new knowledge about healthy brain development.
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The goal of this research unit is to understand the molecular mechanisms leading to neuronal (brain cell) death in Huntington Disease, an incurable genetic disorder that usually strikes in mid-life, causing progressive, irreversible and ultimately fatal neurological damage. With a focus on the fundamental molecular structure and function of neurons, such research also has relevance in understanding the development and effects of other degenerative neurological disorders, such as Alzheimer’s and Parkinson’s Disease, and for understanding recovery from brain injury. As the study of disease reveals information about normal structure and function, this research will also contribute new knowledge about healthy brain development.
This research unit has a focus on the molecular mechanisms leading to neuronal (brain cell) death in Huntington Disease, an incurable genetic disorder that causes progressive, irreversible and ultimately fatal neurological damage. By revealing new information about the fundamental molecular structure and function of neurons, this research will also have relevance in understanding the development and effects of other degenerative neurological disorders (such as Alzheimer’s and Parkinson’s Disease); recovery from brain injury; and healthy brain development.
FIND is committed to the delineation of the molecular pathways that lead to neuronal death in Huntington’s and related disorders, with a particular emphasis on three major sub-themes: proteolysis, excitotoxicity and post-translational modification of target proteins.
A common theme that unites several neurodegenerative disorders is dysfunctional proteolysis, which leads to the accumulation of abnormal protein products that may play a role in, and thus offer a potential therapeutic target for preventing the onset and progression of cell death. Excitotoxicity due to excessive glutamatergic activity and/or age-related mitochondrial dysfunction may also play a role in triggering neuronal death, opening the possibility that interrupting the excitotoxicity pathway may be an effective counter measure. The third sub-theme is directed at exploring evidence that mutant huntingtin alters two proteins that play a key role in the assembly and location of neuronal molecules required for effective receipt and transmission of signals between brain cells. Exploring each of these areas and their inter-relationships holds promise for significant advances in understanding and addressing the complex molecular and cellular interactions that lead to early cell death in neurological disease.
Award term completed September 2009.