WLDs Protein and Ab-Induced Synaptic Dysfunction

Our objective is to elucidate whether a protein (known as WLDs) is functionally useful as a protective factor in an Alzheimer’s Disease model. Given the protective effect that the WLDs protein has had in other models, our working hypothesis is that the protein will attenuate synaptic dysfunction Alzheimer’s Disease models.

Dysfunction at synapses in the brain may underlie many of the deficits present in Alzheimer’s Disease. Factors that influence the health of synapses are thus vital areas of research focus. The proposed research will be focused on a protein which has shown promise as a protective factor in other models of neurodegeneration, but which has not been examined in Alzheimer’s Disease models. Our objective is to elucidate whether this protein (known as WLDs) is functionally useful as a protective factor in an Alzheimer’s Disease model. Given the protective effect that the WLDs protein has had in other models, our working hypothesis is that the protein will attenuate synaptic dysfunction Alzheimer’s Disease models. We will first determine the effects of the WLDs protein on synaptic transmission and learning deficits known to exist in Alzheimer’s Disease models. In the second part of our proposal, we will examine the effect of the WLDs protein on known structural and synaptic protein expression changes in Alzheimer’s Disease models. In the long-term, we hope that the potential protective effects of the WLDs protein will serve to clarify the mechanism of synaptic dysfunction in Alzheimer’s Disease as well as lead to therapeutic options for treating synaptic dysfunction.

Progress Updates

The goal of this study is to elucidate whether the protein (WLDs) is a protective factor in an Alzheimer disease as shown in other neurodegenerative models. We will access this question in two ways. First, we will determine the effects of WLDs protein on learning deficits in known Alzheimer disease model. Second, we will examine the effects of WLDs protein on known abnormality of neural structure in Alzheimer disease model. We have made progress in these two areas: (1) the preliminary results suggested the WLDs protein doesn’t have a protective effect on the Abeta-induced acute learning deficits. We will further test whether the WLDs protein will affect the long term learning deficits and synaptic dysfunction results from Abeta; toxicity in Alzheimer disease model animal; (2) we have established the primary cultured neurons to examine the impacts of WLDs protein on structural and synaptic protein expression changes in Alzheimer disease model. Lastly, our preliminary experiments with complementary techniques continue to support our hypothesis that the potential protective effects of the WLDs protein will contribute to understanding the mechanism of synaptic dysfunction in Alzheimer disease.