Scientists Discover ALS Protein Linked to Cancer and Dementia

TDP43 protein found to regulate critical DNA repair process, with implications for neurodegeneration and cancer

Mar. 15, 2026 at 4:07am

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Researchers at Houston Methodist have discovered that the protein TDP43, which is tied to neurodegenerative conditions like dementia and ALS, also plays a critical role in regulating DNA mismatch repair. The study found that imbalances in TDP43 levels can disrupt this repair process, harming neurons and destabilizing the genome, potentially increasing cancer risk. The findings suggest TDP43 is at the intersection of neurodegeneration and cancer.

Why it matters

This discovery places the TDP43 protein at the center of both neurodegeneration and cancer biology, providing new insights into the underlying mechanisms of devastating diseases like ALS, frontotemporal dementia, and various cancers. Understanding the broader role of TDP43 could lead to new treatment approaches targeting DNA repair processes.

The details

The researchers found that TDP43 regulates genes responsible for fixing DNA errors through the DNA mismatch repair system. When TDP43 levels drop too low or rise too high, the repair genes become overly active, which can harm neurons and destabilize the genome, potentially increasing cancer risk. The team also analyzed cancer databases and found higher TDP43 levels were associated with greater numbers of mutations in tumors.

  • The study was published in Nucleic Acids Research in March 2026.

The players

Muralidhar L. Hegde

Lead investigator and professor of neurosurgery at the Houston Methodist Research Institute's Center for Neuroregeneration.

TDP43

A protein tied to neurodegenerative conditions such as dementia and amyotrophic lateral sclerosis (ALS).

Houston Methodist

The research institution where the study was conducted.

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What they’re saying

“DNA repair is one of the most fundamental processes in biology. What we found is that TDP43 is not just another RNA-binding protein involved in splicing, but a critical regulator of mismatch repair machinery. That has major implications for diseases like ALS and frontotemporal dementia (FTD) where this protein goes awry.”

— Muralidhar L. Hegde, Professor of neurosurgery (Nucleic Acids Research)

“This tells us that the biology of this protein is broader than just ALS or FTD. In cancers, this protein appears to be upregulated and linked to increased mutation load. That puts it at the intersection of two of the most important disease categories of our time: neurodegeneration and cancer.”

— Muralidhar L. Hegde, Professor of neurosurgery (Nucleic Acids Research)

What’s next

The scientists say the findings may point toward new treatment approaches, and that controlling DNA mismatch repair may offer a therapeutic strategy for diseases involving TDP43 imbalances.

The takeaway

This discovery fundamentally changes our understanding of the TDP43 protein, placing it at the intersection of neurodegeneration and cancer. By regulating critical DNA repair processes, TDP43 imbalances may contribute to the development of devastating diseases like ALS, dementia, and various cancers, opening up new avenues for research and potential treatments.