Researchers at Nagoya University are One Step Closer to Unraveling the Tau Mystery in Neurodegenerative Diseases

According to a recent article in MedicalXpress, researchers in Japan led by Dr. Shinsuke Ishigaki and his team at Nagoya University, have identified new molecular details about tau’s activity.

Alzheimer’s, a slow and progressive neurodegenerative disorder associated with tau, was first identified in 1906. The presence of tau protein filaments is connected to certain brain disorders.

Tau has been the focus of numerous studies, especially during the past three decades, but there are still many mysteries surrounding it.

To date, it has become well known that abnormal deposits of Amyloid-beta create plaque in the brain. Its companion, tau, causes tangles that destroy brain cells, resulting in memory loss and problems with reasoning and cognition.

Recently, Dr. Ishigaki’s team discovered complexities that have been hidden in tau’s cellular activities. Their findings may revolutionize treatment for neurodegenerative diseases (tauopathies) that are “tau-induced”.

About Neurodegenerative Diseases

An adult, usually over 60, will show symptoms of frontotemporal lobar degeneration (FTLD) often before the appearance of Alzheimer’s disease (AD). FTLD is a form of dementia associated with speech disorders, mood (affective) disorder, and personality changes.

Both of these disorders are neurodegenerative diseases. Clustering of the tau protein in nerve cells is characteristic of FTLD and AD.

Other examples of tau-induced neurodegenerative diseases would be amyotrophic lateral sclerosis and progressive supranuclear palsy, which is a brain disorder causing difficulty with walking, eye movements, and balance.

Corticobasal degeneration is also included in the group. The disease causes loss of nerve cells and shrinkage of various regions in the brain.

Unraveling the Tau Mystery

Dr. Ishigaki reported that their discovery occurred while focusing on tau and studying FLTD mouse models. That is when they discovered two interacting proteins. One is FUS (fused in sarcoma), and the other is (SFPQ) splicing factor, proline-and glutamine-rich.

According to Dr. Ishigaki, these two proteins are critical for functional tau generation.

About the Study

The team’s examinations indicate that an abnormality taking place in the RNA-binding proteins SFPQ and FUS in neurons, as well as changes in tau isoform composition, are underpinnings to a group of dementias called FTLD spectrum diseases.

Tau isoforms are produced by the splicing of the MAPT gene, which encodes tau proteins and is regulated by FUS and SFPQ, RNA-binding proteins.

FUS and SFPQ were studied in the brain samples of 142 deceased patients who had neurodegenerative diseases. Their findings led them to create a novel model of “imbalanced accumulation of tau” in cells.

In the new model, SFPQ and FUS monitor MAPT processing, which is the encoding gene for tau and the genetic region called exon 10.

Their report on the unique role of tau, specific for the FTLD spectrum, was published in the August 7, 2020 edition of the journal Brain. Dr. Ishigaki points out that these mechanisms contribute to FTLD and ALS disorders but it does not include Alzheimer’s or Pick’s disease.

Dr. Ishigaki explains the importance of this discovery. Now, knowing the way in which tau causes FTLD spectrum diseases, a path to treatment strategies is created that may target factors connected to the process such as FUS/SFPQ proteins.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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