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2010 Grants - Iijima-Ando
Tau Phosphorylation and Toxicity Induced by Mitochondrial Mislocalization
Kanae Iijima-Ando, Ph.D.
Thomas Jefferson University
2010 New Investigator Research Grant
The protein tau normally plays an important role in maintaining brain cell structure. Tau is usually modified by a process called phosphorylation, or the attachment of phosphate molecules. But in Alzheimer's disease, tau becomes excessively phosphorylated and loses its ability to carry out its normal functions. Growing evidence also suggests that excessively phosphorylated tau plays a vital role in the earliest stages of Alzheimer's. Yet the mechanisms by which abnormal tau exerts its toxicity remain unknown.
Recent studies have shown that cellular structures called mitochondria, which help produce energy for a brain cell, make the cells more vulnerable to Alzheimer toxicity when they become transported to improper cellular locations. Kanae Iijima-Ando, Ph.D., and colleagues have been studying the pathological roles of mitochondria in fruit flies engineered to develop tau-related pathologies. The researchers found that tau-induced brain damage is enhanced when the cellular transport of mitochondria becomes abnormal. The team also found that reduced mitochondrial transport increases tau phosphorylation in cells known to suffer Alzheimer damage.
Based on these earlier findings, Dr. Iijima-Ando and colleagues hypothesize that abnormal mitochondrial transport promotes tau toxicity in cells by enhancing tau phosphorylation in certain disease-affected brain regions. The researchers plan to test their hypothesis in this proposed grant. They also plan to look for any mechanisms that may underlie the connection between mitochondrial misplacement and tau toxicity. For both of these experiments, the team will continue to use fruit fly brains.
The results of this study could shed new light on how Alzheimer's disease develops at its earliest stages. Such work could lead to novel preventative strategies for the disease.