Core Causal Mechanism of Tau-Induced Neurodegeneration Discovered!

Novel discovery of the root cause of tau-induced neurodegeneration may help in formulating tailored drug targets for Alzheimer’s disease and related dementias.

Novel pathological mechanism of tau protein has been unraveled by a study at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), published in Alzheimer’s & Dementia.

Tau protein pathology includes the accumulation of abnormal tau proteins that results in gradual neuronal death. Disorders include Alzheimer’s disease, chronic traumatic encephalopathy (CTE), and more than 20 similar disorders.

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‘Novel discovery of the root cause of tau-induced neurodegeneration may help in formulating tailored drug targets for Alzheimer’s and related dementias.’

The new mechanism may be explored pharmacologically to formulate a novel target for drug development against tau pathology.

“The fact it is a druggable target is really exciting, and it is a new mechanism that wasn’t previously established,” says Gabrielle Zuniga, first author and an MD/PhD student in the South Texas Medical Scientist Training Program.

Novel Tau Mechanism

It was found that deficits in an RNA quality-control pathway — nonsense-mediated mRNA decay was described as an early event, that occurred long before neuronal cell death in tau-mediated cell damage.

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“Nonsense-mediated mRNA decay is a key step in the process by which genetic information is translated into proteins.” Impairment of this quality-control mechanism results in buildups of RNA and production of abnormal, dysfunctional proteins. “It has an absolutely detrimental effect,” says Zuniga.

The study thereby suggests that targeting a much earlier mechanism — mRNA decay pathways rather than targeting a later disease process — tau deposition may seem as a promising yet brilliant discovery against various tau pathologies that may aid in formulating novel therapies.

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