Ralph A. Nixon PhD, MD

Dr. Ralph A. Nixon was a major neurodegenerative disease, such as Alzheimer’s and Parkinson’s, the abnormal accumulation of one or more polypeptides within or around neurons is central to pathogenesis. Our research focuses on two aspects of neurobiology that govern the fate of normal and pathogenic proteins: the regulation of proteolytic processing and the control of protein export into axons and synapses. We have identified dysfunction of the endosomal-lysosomal system, involving altered endocytosis and mistrafficking of proteases to endosomes, as the earliest known pathological response of neurons in Alzheimer’s disease.

Dr. Ralph A. Nixon our cell modeling studies show early endosomes to be major generators of the toxic ß-amyloid peptide and implicate dysfunction of endosomes in the mechanism of SS-amyloid accumulation in "sporadic" Alzheimer’s, the most common form of the disease. Genetic manipulations of proteolytic systems in mice are being used, together with cell culture models, to determine the consequences of endosomal-lysosomal and calpain system dysfunction on the processing of Alzheimer-related proteins, receptor-mediated signal transduction, and neuronal cell death pathways.