Scientists at the University of New Mexico and University of Tennessee have discovered that the brain enzyme OTULIN plays an unexpected role as a master regulator of tau protein production and RNA metabolism in neurons. While investigating how to clear toxic tau tangles characteristic of Alzheimer's disease, researchers found that eliminating OTULIN caused tau to disappear completely—not through enhanced degradation, but by preventing its gene from being expressed. The study, published in Genomic Psychiatry, revealed that when OTULIN was knocked out in neuroblastoma cells, it triggered massive changes in gene expression (13,341 genes downregulated, 774 upregulated) and fundamentally altered how neurons process RNA. Comparing Alzheimer's patient neurons to healthy controls showed over 4,500 differentially expressed genes. Partial inhibition of OTULIN with a novel compound (UC495) reduced pathological tau in Alzheimer's patient neurons without complete elimination, suggesting a therapeutic window exists. This paradigm-shifting discovery identifies OTULIN as a potential drug target for Alzheimer's and related dementias, though researchers emphasize the need for careful modulation rather than complete inhibition. The findings also illuminate previously unknown connections between protein quality control systems, RNA metabolism, and neurodegenerative disease.

USC researchers have uncovered new insights into how brain wiring differs in children and young adults with autism, pointing to more precise ways of understanding the condition. The study, published in Cerebral Cortex, analyzed brain scans from 365 participants between the ages of 5 and 24. Using advanced imaging and informatics methods, the team mapped tiny structural differences in the brain’s white matter, the “communication highways” that connect different regions of the brain. Traditional imaging studies have suggested differences in white matter in autism, but results have been inconsistent. To address this, the team applied new computational tools that allow for fine-scale mapping along individual fiber bundles. They found that, on average, autistic participants showed localized changes across many major tracts that link the brain’s hemispheres and connect regions involved in language, social behavior, and sensory processing.