Tau Causes Neuronal Death through Mitochondrial Pathology

Mel B Feany, MD, PhD
Brigham and Women's Hospital (Boston, MA, United States)
Year Awarded:
Grant Duration:
July 1, 2012 to September 30, 2013
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern
Mel B Feany, MD, PhD

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.

About the Researcher

Mel B. Feany, M.D., Ph.D., is a Professor of Pathology, Harvard Medical School and Brigham and Women’s Hospital. Feany’s laboratory models human neurodegenerative diseases in Drosophila melanogaster (commonly known as a “fruit fly”)—an organism that can have diseases similar to humans and has a fully sequenced genome. Her laboratory has previously engineered flies to have human forms of tau related to Alzheimer’s disease and Parkinson’s disease and found them to have human-like symptoms. Feany’s team has subsequently used Drosophila genetics, along with validating experiments in vertebrate model systems (including mice engineered to have these diseases), to identify cellular and molecular pathways mediating neuronal death in Alzheimer’s disease and related neurodegenerative disorders.


DuBoff B, Götz J, Feany MB. Tau promotes neurodegeneration via DRP1 mislocalization in vivo, Neuron, 2012;75:618-32. PubMed Icon Google Scholar Icon

DuBoff B, Feany M, Götz J. Why size matters - balancing mitochondrial dynamics in Alzheimer's disease. Trends Neurosci. 2013;36:325-35. PubMed Icon Google Scholar Icon

Merlo P, Frost B, Peng S, Yang YJ, Park PJ, Feany M. p53 prevents neurodegeneration by regulating synaptic genes. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):18055-60. doi: 10.1073/pnas.1419083111. Epub 2014 Dec 1. PubMed Icon Google Scholar Icon

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