Project 174440

Amyloidoses involve the abnormal deposition of protein fibrils or plaques within tissues leading to extensive cellular damage. Amyloid plaques are associated with a number of disorders including Alzheimer's disease and type-2 diabetes which are the focus of our research program. Although each is unique, all amyloid proteins can under certain conditions assemble in to morphologically and structurally identical fibrillar or thread-like structures. This suggests that amyoid deposits are formed by similar mis-folding pathways and therefore therapeutic interventions to control these events may be beneficial for these diseases. We propose to address this problem with a comprehensive strategy that will combine biophysical and biochemical approaches to the development of amyloid inhibiting drugs for the treatment of diabetes. This will be accomplished in conjunction with the development of cellular novel models that recreate the pathological features associated with type-2 diabetes and provide test vehicles for the evaluation of these drugs. Our ultimate goals are to understand the causes of diabetes and to develop a means to prevent or delay the progression of the disease.