Tau protein tangles in the brain are a hallmark of Alzheimer’s disease, but recently these vital filaments have gained an undeserved bad guy reputation.
Like the story of Dr. Jekyll and Dr. Hyde, Tau’s story is a complex mix of good and evil.
A surprising new study of fly and rat brain cells suggests that the tau protein normally protects the brain from degeneration — only when it is absent or defective does it seem to contribute to brain disease.
“By revealing a surprising new neuroprotective role for tau, this study opens the door to potential new strategies to slow, reverse and treat neurodegenerative diseases.” say Hugo Belén, a neuroscientist at Baylor College of Medicine in the US.
The findings of this study are: Root Cause Alzheimer’s disease is Lipid droplets In the connective tissue of the brain.
These lipid droplets are like garbage bags for neuronal waste: When neurons need to get rid of toxic substances such as reactive oxygen species (ROS), they pump that waste to nearby cells called glia, which package the ROS in lipid droplets.
“This process effectively removes and neutralizes these toxic lipids.” explain Lindsay Goodman, a neurobiologist in the Belen lab.
However, in the absence of tau protein in fly glial cells, these lipid droplets do not form, and toxic ROS build up in the brain, causing movement disorders.
Goodman and his colleagues found that a loss of even 50 percent of healthy tau was enough to disrupt lipid droplets and cause toxicity in the fly brains.
Similar effects were seen in rat and human glial cells, suggesting that tau also plays a neuroprotective role in mammals like us.
The findings suggest an entirely new benefit of tau. These proteins It is abundant in the human brain and is found in healthy people. Fold and tie This is to create the internal “skeleton” of the brain cells.
But when tau is missing or mutated, it doesn’t fold properly and problems start to occur.
In a “humanized” fly model harboring the same tau mutation seen in some cases of Alzheimer’s disease, the researchers found that the tau protein was no longer able to combat rising ROS levels.
When ROS were increased in the experiments, glial cells in flies carrying mutant tau showed severe damage.
the study The authors say their findings provide “compelling evidence” that tau loss is only deleterious in the presence of ROS, which could potentially This explains why mice genetically programmed to lack tau do not show signs of neurodegeneration until old age, when ROS levels begin to accumulate.
In other words, it’s not just the lack of healthy tau that causes the problem. It’s how the lack of healthy tau interacts with the proliferation of toxic by-products in the brain.
“Low levels of ROS are beneficial, but excess ROS are harmful to cells because they induce the production of toxic forms of other molecules that cause oxidative stress.” explain Goodman.
In recent years, misfolded tau protein Appeared As one of the earliest biomarkers of Alzheimer’s disease, Can damage or kill neurons But scientists are still unsure whether these tangles are the root cause of neurodegeneration, or whether Addressing other underlying issues.
Tau tangles are found in some of the brains of people who have died from Alzheimer’s disease, but the mutated protein I can’t fully explain it The different subtypes of this neurodegenerative disease.
Over the past 17 years, Over 30 types of medicine Target Tau achieved Clinical Trials After showing promise in animal models, None of them are profitable In human patients.
New research suggests that attacking all forms of tau across the board may eliminate the “good” tau along with the “bad” tau.
When it comes to tau-related brain diseases, nuance seems to be the key.
This study Nature Neuroscience.
