How the protein tangled in "Neuron" kills brain cells step by step and induces Alzheimer's disease

Abnormal levels of beta-amyloid in the brain form plaques (brown in the picture) between neurons, destroying cells

If you delve deeper into the brains of patients with Alzheimer's disease, you will find a common suspected culprit: a fibrous, hairy globular protein tang called tau

These diseases are collectively referred to as "tau disease" and have attacked many people worldwide

But more than a century after German psychiatrist Alois Alzheimer discovered tau tangles, scientists still have a lot to learn

A study published in the journal Neuron by the University of Colorado Boulder (University of Colorado Boulder) showed for the first time that tau protein accumulates in cells to phagocytize RNA and interfere with an overall mechanism called splicing.

"Understanding how tau protein causes neurodegeneration is not only the key to understanding Alzheimer's disease, but also the key to understanding many other neurological diseases," said Roy Parker, director of the BioFrontiers Institute and professor of biochemistry.

The research was led by Evan Lester, a candidate for the Doctor of Medicine in the Medical Scientist Training Program

Lester said: "At present, we can do nothing about these patients-there is no disease modification treatment for Alzheimer's disease or most other tau diseases

In this study, the researchers isolated tau aggregates from cell lines and the brains of mice with Alzheimer-like disease

They confirmed for the first time that tau protein aggregates contain RNA, a single-stranded molecule that synthesizes proteins in cells

They also found that tau protein interacts with fragments of cellular machinery called nuclear spots, isolates and replaces their internal proteins, and disrupts the RNA splicing process.

"The tau aggregates seem to isolate splicing-related RNA and proteins, disrupt their normal functions, and impair the cell's ability to make proteins," Lester said

It is worth noting that when scientists examined the brains of Alzheimer's patients after death, they found evidence of splicing-related defects in the cells

Several companies are already conducting clinical trials to test drugs that completely eliminate tau protein in patients with neurodegenerative diseases

He said: "A big problem in this field is that no one really knows what role tau protein plays in healthy people.

A more accurate understanding of its damage and killing effects on cells can lead to a different approach
.

Lester said: "Our idea is to intervene in abnormal functions while preserving the normal function of tau protein
.
"

Although his current patients are unlikely to benefit from his findings, one day his future patients may benefit
.

"Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components" by Evan Lester, Felicia K.
Ooi, Nadine Bakkar, Jacob Ayers, Amanda L.
Woerman, Joshua Wheeler, Robert Bowser, George A.
Carlson, Stanley B.
Prusiner and Roy Parker, 12 April 2021, Neuron .