Research Grant Award

Stefan Kindler, PhD

University Medical Center, Hamburg, Germany
Spinocerebellar ataxia 2: cellular and molecular action of normal and mutant ataxin-2

Ataxia, an unsteady and clumsy motion of the limbs and torso, is a common disability accompanied by severe loss of quality of life and often premature death. Different types of inherited spinocerebellar ataxias (SCAs) are caused by mutations in distinct genes. In several diverse forms of SCA, these mutations lead to expansions of so-called polyglutamine (polyQ) stretches in the corresponding gene products, termed proteins. Proteins are organic compounds composed of a chain of different amino acids, including one called glutamine. They are the main molecular working units of cells and participate in practically every cellular process often via regulated interactions between particular proteins. Each protein possesses a precise three dimensional structure that enables it to fulfill its specific cellular function. Most structural alterations thus lead to functional deficits. Spinocerebellar ataxia type 2 (SCA2) is caused by a
polyQ stretch expansion in a protein named ataxin-2. This alteration may compromise the structure and cellular interaction pattern of ataxin-2 and disrupt its physiological function thereby causing the death of particular brain cells, which finally results in uncoordinated muscle movements. Our research aim is to identify proteins, which interact with normal ataxin-2 in cells. These data will help to determine the cellular function of ataxin-2. In addition, we will analyze whether polyQ expansion changes the interaction pattern of ataxin-2. Identified differences may help to understand the cellular mechanism by which the altered protein leads to the development of the disease. In the long term, our studies are aimed at designing new therapies to delay or prevent the progress of ataxia in individuals affected by SCA2.