Mitochondrial Pathology in Tauopathy

In this study, Dr. Mel B. Feany and her team use clues from genetic screens to develop a detailed understanding of the mechanisms by which tau becomes toxic to neurons in Alzheimer’s disease and related tauopathies. In particular, they are studying the influence of mitochondrial biology on neurotoxicity. These tests, if successful, would pave the way towards consideration of mitochondrial function and dynamics as attractive potential therapeutic targets in Alzheimer’s disease, as well as related tauopathies.

We do not currently have highly effective treatments for Alzheimer’s disease. Thus, searching for treatments is a high priority in Alzheimer’s disease research. Although research over the past two decades has been very successful and has identified some potential targets for drug development, there remains a great need for identification of additional proteins that can serve as future drug targets.

Dr. Mel B. Feany and colleagues are focusing on how tau causes the energy powerhouse of the cell, the mitochondrion, to malfunction. Their preliminary data suggested that mitochondria in disease states become too long, and subsequently cannot provide the cell with the energy and other factors it needs to survive. In this study, the researchers are determining precisely which proteins work together to maintain normally functioning mitochondria.

Part of the study will tease apart how the protein tau, strongly implicated as being toxic in Alzheimer’s disease and related neurodegenerative disorders, disrupts the delicate cellular machinery that maintains proper mitochondrial length and function. This work is innovative in that no one else has identified the control of mitochondrial length as a specific process disrupted by tau to cause neuronal death. Thus, the proteins and interactions being characterized in these experiments are a prelude to the development of unique new targets in the critical ongoing efforts to develop effective drugs to treat Alzheimer’s disease.