USC Stem Cell scientists discover a new way to rid cells of toxic tau protein in a study involving mice and lab-grown human “mini-brains,” known as organoids.
The neurotransmitter glutamate is essential for regulating everything from mood to memory, but it can also encourage a toxic buildup of the notorious tau protein, which can contribute to Alzheimer’s and related diseases. In a USC Stem Cell-led study published in Neuron, scientists describe a new approach for counteracting these devastating and often fatal neurodegenerative effects.
In the study, first authors Joshua Berlind and Jesse Lai made their discovery by studying lab mice as well as human brain “organoids,” which are rudimentary brain-like structures grown in the lab. The scientists produced these organoids from stem cells derived from healthy people as well as from patients with neurodegenerative diseases related to tau toxicity.
When exposed to glutamate, the organoids—particularly the ones derived from patients with neurodegenerative diseases—exhibited a toxic buildup of tau protein as well as neurodegeneration and nerve cell death. Mice with a mutation in tau, which causes a common form of dementia, displayed similar pathologies.
“Many potential drugs have been developed to mitigate the neurodegenerative effects of glutamate toxicity, but they’ve had mixed results in clinical trials,” said corresponding author Justin Ichida, who is the John Douglas French Alzheimer’s Foundation Associate Professor of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC, a New York Stem Cell Foundation-Robertson Investigator, and a USC Merkin Scholar. “One challenge is that directly limiting the activity of glutamate, a key neurotransmitter, can have negative consequences, such as motor or memory deficits or even reduced consciousness.”
To read more, visit https://stemcell.keck.usc.edu/how-to-clear-the-toxic-tau-protein-that-can-lead-to-alzheimers.