HSP--also known as familial spastic paraparesis and Strumpell-Lorrain syndrome--causes the ends of the nerves that control muscle activity to deteriorate. These nerve cells run from the brain's cerebral cortex to the spinal cord where they connect to "downstream" nerve cells that excite muscles throughout the body to control coordinated movement. HSP causes weakness, spasms and loss of function in the muscles in the lower extremities.
More than 20 genes have been linked to HSP. However, more than 40 percent of all cases have been traced to a single gene (SPG4) that produces an enzyme called spastin. Previous studies have shown that this enzyme interacts with microtubules, the tiny protein tubes that provide structural support and transport avenues within most cells. Microtubules are dynamic structures, continually growing and shrinking, and their stability is closely regulated by a number of associated proteins. In nerve cells, microtubules carry cellular components to distant regions of the cell, regulate the growth of cellular branches and provide a substrate for important protein interactions. All of these functions are critically dependent on dynamic changes in microtubule stability.
Researchers in the laboratories of Kendal Broadie at Vanderbilt University and Andrea Daga at the University of Padova, Italy, collaborated on the first studies of the role that spastin plays in nerve communication in a living organism. Th
Contact: David F. Salisbury