Recent studies have shown that the entanglement of tau protein causes Alzheimer's disease. Many therapies attempt to target the producing and eliminating of tau protein to treat the disease. Actually the role of tau protein in other neurodegenerative diseases has also been studied. For example, tau fragments are proved to participate in maintaining genomic stability and chromosomal integrity.

A multi-agency study led by researchers at Massachusetts General Hospital (MGH) and Johns Hopkins School of Medicine found that abnormal forms of tau protein accumulated in neurofibrillary tangles, which is a striking feature of Alzheimer's disease, can destroy the normal function of brain cells. In their report in the journal Neuron, the team described how tau protein interferes with the communication between nerve nuclei and cytoplasm.

"Communication between the nucleus and the cytoplasm is usually a highly regulated process," said co-senior author Bradley Heyman. "Our work shows a new way in which tau can cause damage to brain cells. In other systems, the disruption of this communication can lead to cell dysfunction and even cell death, so we believe this may lead to neuronal dysfunction and death in Alzheimer's disease."

A recent study by the Hayman team found a new biochemical feature of tau that can form microscopic droplets. By looking for other proteins with this property, the researchers finally got the constituent proteins of the nuclear pore complex. They set out to investigate whether and how tau interacts with proteins in the nuclear pore complex.

Small molecules can pass freely through the nuclear pore complex, but larger molecules need to be actively transported through the interaction between the receptor protein and the nuclear pore protein on these molecules. Whether the molecule moves into the nucleus depends on the shuttle of the RanGTPase between the nucleus and the cytoplasm. Previous studies have reported several neurodegenerative diseases as well as nucleosome transport in neurons in normal aging.

In experiments with neuronal and tau-based neuropathological cell models in patients with Alzheimer's disease, the researchers found that Alzheimer's-associated tau interacts directly with an important nuclear pore protein called Nup98. This interaction causes Nup98 to erroneously localize into the cytoplasm, facilitating tau aggregation into neurofibrillary tangles. In addition, neuronal nuclei from patients with Alzheimer's disease absorb a large number of test molecules, indicating that the nuclear pore complex has leaked. The number of structures is also reduced and unevenly distributed throughout the nuclear membrane.

Neurons from the genetic model of tau brain-entangled mice also showed similar nuclear pore complex leakage, allowing large dye molecules to enter the nucleus. The level of Ran enzyme disappears from the neuron nucleus of the animal, which also shows changes in shape and structure. Inhibition of abnormal tau gene expression restored the levels of Ran and Nup98 in the nuclear membrane, suggesting that tau is responsible for Ran abnormalities.

"One of the exciting things about these findings is that if we can prevent the interaction between tau and the nuclear pore, it may enhance the function of neurons in the patient.”

Tau mutations serve as a novel risk factor for cancer.

Previous analysis of peripheral cells and related animal models of patients with frontotemporal degeneration with tau gene mutation revealed abnormalities such as chromosome number and structure. Because the instability of the genome is closely related to the development of cancer, scientists from Italy suggest that the mutant tau protein may be a susceptibility factor affecting cancer, and this hypothesis is further proved. The results of the study are published internationally in the academic journal Cancer Research.

In this study, the researchers conducted a retrospective cohort study comparing cancer incidence in families and control families carrying tau mutations, in addition to bioinformatics analysis of tau protein. There are signal pathways for interaction. The results of the study showed that the incidence of cancer in the tau gene mutation family was significantly higher than that in the control family, and a high proportion of proteins interacting with tau protein were involved in cancer-related cellular processes.

These findings reveal that in addition to the development and progression of neurodegenerative diseases, tau can also play a new role in cancer risk factors, which provides important information for a more comprehensive understanding of the physiological role of mutant tau.

Author's Bio: 

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