Breakthrough in Protein Complex Research Could Lead to New Treatments for Huntington's Disease

Researchers from Thomas Jefferson University have made a significant discovery that sheds light on the molecular mechanisms behind Huntington's disease, a genetic disorder characterized by the progressive death of nerve cells in the brain. Led by Dr. Anna Pluciennik, the team identified a specialized protein complex involved in repairing abnormal DNA sequences that are central to the disease's development. The study focused on the interaction between two proteins, FAN1 and PCNA, which work together to identify and snip off extra loops in DNA caused by the repetitive genetic mutation associated with Huntington's. Using advanced electron microscopy techniques, the team visualized how FAN1 acts like molecular scissors, effectively cutting away these harmful DNA loops when partnered with PCNA. Importantly, mutations affecting the stability of this complex were linked to earlier disease onset, suggesting that enhancing the stability or abundance of FAN1 could delay disease progression. The findings position the FAN1-PCNA complex as a promising target for future therapeutic strategies aimed at mitigating the effects of Huntington's. This research contributes to a deeper understanding of how genetic and molecular factors influence neurodegeneration and highlights new avenues for potential treatments.