Research Grant Award

Research Fellowship Award

Strauss, Karsten, PhD

Cedars-Sinai Medical Center, Los Angeles, CA
SCA 2 Pathogenesis: Altered splicing caused by gain of normal ataxin-2 function

Spinocerebellar ataxia 2 (SCA2) is an inherited neurological movement disorder caused by mutation in the ataxin-2 gene. The disease is caused by a progressive loss of cells in a region of the brain that controls balance and motor function. Patients have a decrease in fine movement coordination, speech problems and uncontrolled eye movements resulting in an escalating impairment of daily living during the course of the disease. Although the disease gene was identified 10 years ago, the precise mechanisms leading to neuronal dysfunction and nerve cell death have remained elusive. Several years ago, we discovered a protein that binds to atxn2 designated A2BP1 or fox-1. Recently, the function of this protein has been unravelled pointing to a role in processing of messenger RNA and potentially in guiding and stabilizing messenger RNA in specific compartments of the cell. Based on our discovery of interaction of A2BP1 and atxn2, we are no proposing to examine the effects of mutant atxn2 on the processing of messenger RNAs. We hypothesize that mutant atxn2 prevents A2BP1 from its proper function in the nucleus of the cell. We will examine this hypothesis by interaction studies of normal and mutant atxn2 with A2BP1. We will then determine whether mutant atxn2 will cause faulty processing of messenger RNAs. These studies may have general implications for understanding the role of mRNA processing in neurodegeneration, but will also open the door for designing specific therapies for SCA2.