The Aryavarth Express
Washington, DC: Researchers at Houston Methodist Research Institute have identified a protein associated with neurodegenerative disorders that also plays a key role in a vital DNA repair process, potentially linking brain diseases and cancer.
The study, published in the journal Nucleic Acids Research, reveals that the protein TDP43 regulates genes responsible for fixing errors that occur when cells replicate genetic material. This repair system, known as DNA mismatch repair, corrects mistakes made during DNA copying.
According to researchers, abnormal levels of TDP43—either too high or too low—can disrupt the balance of this repair mechanism. Instead of protecting cells, excessive repair activity may damage neurons and destabilize the genome, potentially increasing the risk of both neurodegenerative diseases and cancer.
Lead investigator Muralidhar L. Hegde said the findings expand the understanding of the protein’s biological role.
“DNA repair is one of the most fundamental processes in biology,” Hegde said. “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 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia where this protein becomes dysfunctional.”
The research team also discovered a potential link between TDP43 and cancer. By analyzing large cancer databases, scientists found that higher levels of the protein were associated with an increased number of mutations in tumors.
Hegde explained that the results place the protein at the intersection of two major disease categories—neurodegeneration and cancer—suggesting its biological influence may be broader than previously believed.
The findings could also open new avenues for treatment. In laboratory models, scientists observed that reducing excessive DNA repair activity caused by abnormal TDP43 levels helped partially reverse cellular damage.
Researchers believe that targeting the DNA mismatch repair pathway may offer a potential therapeutic strategy for conditions linked to abnormal TDP43 activity.
