Study reveals why rare neurological disease damages specific brain regions

Many neurological diseases damage specific parts of the brain, even though the harmful protein involved is present throughout the brain. Researchers at Texas Children's Duncan Neurological Research Institute (Duncan NRI) and Baylor College of Medicine report in Genes & Development new evidence that explains these differences in brain tissue vulnerability.

Working with animal models of human spinocerebellar ataxia type 1 (SCA1), the team showed that different forms as well as levels of partner proteins involved in the disease can lead to distinct molecular interactions and biological outcomes in different tissues. The findings, which could be applied to other conditions, suggest that directing therapies to specific protein forms may improve treatment.

"SCA1 is a rare neurodegenerative disorder characterized by progressive loss of coordination (ataxia), slurred speech and swallowing difficulties, which result from damage to the cerebellum, the brain region that controls coordination and balance," said Dr. Huda Zoghbi, corresponding author and Duncan NRI Founding Director, who is also a Distinguished Service Professor at Baylor College of Medicine and an Investigator with the Howard Hughes Medical Institute.

A mutation in the ATAXIN-1 (ATXN1) gene causes SCA1. This mutation produces a faulty protein that is overly active and accumulates inside cells, damaging them. Although the human ATXN1 gene is expressed in many brain regions and other parts of the body such as the heart and the liver, the cerebellum and the brain stem are the most vulnerable to the harmful effects of defective ATXN1 protein.