Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

Intense laboratory and clinical research have failed to discover effective treatments to delay the onset or progression of any neurodegenerative conditions, including those caused by infectious prions. Although prion diseases are rare and uniquely infectious, they share many common features on a sub-cellular level with other neurodegenerative diseases that are much more prevalent in the population such as Alzheimer's disease. The most obvious similarity is the strong association with the accumulation of misfolded and insoluble forms of normal host proteins in the brains of patients. This process triggers progressive genetic changes that eventually lead to profound neuronal damage or death, however, the molecular mechanism that underlies neurotoxicity remains unresolved. It has become clear that profound changes in the brains of patients are evident long before clinical symptoms and it is at this stage at which the disease is reversible, and therefore presents 'druggable' targets. Our research effort is focused on understanding the molecular underpinnings of these early steps in disease pathogenesis. We have established methods to dissect individual neurons from the brains of rodent models of neurodegenerative disease and study alterations using a variety of techniques. Our unique observation is that small genetic regulators, called microRNAs, are induced in neurons at very early stages of prion disease. Evidence suggests that these play roles in neuron regeneration and or survival. Understanding their functions in greater detail will determine whether these molecules can be manipulated to induce regeneration as a therapeutic strategy.