Schipper, Hyman M
Jewish General Hospital (Montreal)
Canada
Role of HO-1 in Aging & Parkinsonian Neural Tissues III
CIHR
490,048
01/04/2013
5
Parkinson disease (PD) is the second most common neurodegenerative disorder in the developed world. Although several drugs are available to alleviate some of the symptoms of PD (such as tremor or stiffness), we sorely lack medications which slow the destruction of nerve cells in the affected brain regions. Two abnormalities observed in the PD brain which are thought to contribute to nerve cell damage in this disease are 1) the excessive accumulation of iron and 2) injury to mitochondria, the cells’ power generators. Our laboratory has collected evidence that both of these abnormalities may be caused by an enzyme called heme oxygenase-1 (HO-1) which is overactive in the brains of PD patients. We recently created a mouse model that mimics the increased brain HO-1 seen in individuals with PD. In the current proposal, we will document the deleterious effects of this excessive HO-1 on the structure and chemistry of the brain and the behaviour of the animals. We will then try to cure these mice and other experimental models of PD with medications that purge the brain of excess iron and a new drug we are developing that blocks the action of HO-1. If successful, this study may herald a novel and rational approach to the prevention of brain cell loss in PD and provide fresh hope to sufferers of this debilitating condition.