FunGen-AD-funded research discovers new functions of tau proteins in neurodegenerative diseases

Tau protein accumulation is a common feature of neurodegenerative diseases like Alzheimer’s disease (AD). A publication from a group of researchers, including FunGen-AD researchers Lindsey Goodman, Hugo Bellen, and Josh Shulman from Baylor College of Medicine and the Duncan Neurological Research Institute of Texas Children’s Hospital, provides new evidence that the tau protein has protective effects in the brain.

Previous work from the Bellen lab showed that high levels of reactive oxygen species (ROS) in neurons lead to production of toxic peroxidated lipids (LPOs). Normally, neurons export these toxic LPOs to neighboring glial cells, which incorporate them into lipid droplets (LDs) for storage and future energy production. The recent publication focused on the role of tau protein in LD formation. Using a fruit fly model, the researchers showed that loss-of-function disrupts formation of LDs, leading to high ROS in the brain, and causing neuronal damage and motor defects. Comparable results were observed in rat and human glial cell culture experiments and fruit flies with AD-associated tau mutations. These results demonstrate that tau protein protects against toxic effects caused by ROS. Interestingly, overexpression of tau in glia also disrupted the formation of LDs, increased levels of ROS, and damaged neurons in fruit flies and in rat neuronal and glial cell culture experiments. Overall, these results show that tau protects against ROS-mediated damage and regulates formation of LDs in a dosage-sensitive way: too much or too little tau is detrimental. This study offers a newly discovered role for tau and a potential therapeutic option to regulate tau levels that support neuroprotection.

This research, partially supported by FunGen-AD grant U01AG072439, is published in Nature Neuroscience here. You can read more about these research findings at the following links: