Argentine

Role of RAGE in central nervous system abnormalities: diabetes and the development of Alzheimer’s disease

Le sommaire ci-dessous est présenté dans la langue de la demande soumis par les demandeurs du concours SCR-CALA.

Diabetes, a chronic disease characterized by high levels of blood sugar, once was a disease that began as people approached their 60s. Now diabetes is occurring in younger age groups and affects more than 300 million people worldwide and nearly two million Canadians over the age of 12. Diabetes is a chronic disease that impacts quality of life and shortens life expectancy by triggering devastating health complications.

Chronic hyperglycemia has been associated with cognitive impairment and brain structural changes, and epidemiologic studies suggest an important correlation between type II diabetes and the progression of Alzheimer’s disease. Even though Alzheimer’s disease can only be influenced to a limited extent, optimal treatment of diabetes may have also a positive effect on Alzheimer’s disease. Thus, understanding the mechanisms involved in the deleterious effects of hyperglycemia in the brain becomes a critical issue, such as the study of common intracellular pathways that can lead from diabetes to Alzheimer’s disease.

Therefore, the objective of this proposal is to understand mechanisms that underlie neuronal impairment during elevated glucose conditions, including regulation of axonal transport dynamics, changes in protein localization, modulation of neurotransmitter receptors and synaptic transmission. We will particularly concentrate in the Receptor for Advanced Glycation End-products (RAGE), which has been identified at the centre of the pathological scenario developed in both diabetes and Alzheimer’s disease. The ultimate goal of this project is to contribute to a better understanding of pathological processes that affect the central nervous system in order to identify new therapeutic strategies for the treatment of neurodegenerative disorders.