Grant: CIHR/Regional Partnership Program/Operating Grants

Alzheimer's disease is thought to be caused by cumulative effects of beta-amyloid that can result in structures in the brain known as plaques and tangles. The plaques often consist of beta amyloid, as well as other proteins that can include those that are increased with stress. The tangles, also known as neurofibrillary tangles (NFTs) can be made of proteins that provide integrity to the neuronal processes or axons; these include proteins such as neurofilaments and the microtubule-binding protein knonw as tau. A group of proteins known as the Heat Shock Proteins (Hsps) are often increased in cells in response to various different stresses. One of these proteins, the small heat shock protein, Hsp27, has been shown to protect various cell types against different agents that could cause cellular damage. With respect to Alzheimer's Disease, Hsp27 has been reported to be increased in AD brains, with accumulation in plaques and tangles. Whether this is a protective response to the stress or is part of the disease process is not known. While most brain neurons do not express Hsp27, there are some selective populations that do. Are these neurons less vulnerable to the cumulative effect of a life time of stressors? In our experiments we can increase the expression of Hsp27 in neurons and have been able to show that this prevents neuronal death triggered by exposure to beta-amyloid. However, we do not know how this occurs and our objectives are to understand how Hsp27 functions and how its expression might be regulated in brain neurons.