Multiple sclerosis and the genes and proteins of central nervous system myelin

A prevalence study of MS in the Channel Islands was undertaken. This showed the prevalence rates to be similar to other south British studies, with a slightly lower (but not statistically significant) rate for women in the Bailiwick of Guernsey.The finding that receptors for known neurotransmitters and proteins involved in signal transduction such as the heterotrimeric G proteins and low molecular weight GTPases are present in myelin shows that little is known about active processes occurring in the myelin membrane. The rho group of proteins are of particular interest as they have a clear role in complex membrane structures such as ruffles, lamellipodia and filopodia as well as actin stress fibre formation. They are good candidates for a role in a complex membrane such as myelin.This led to an attempt to enumerate the number of low molecular weight GTPases in myelin and to identify some of these proteins so as to suggest functional roles for them. A large number of low molecular weight GTP binding proteins were shown to be in both rabbit and in human myelin, using two-dimensional protein electrophoresis, electroblotting, binding to GTPγS and autoradiography. Members of the rho family were then identified as being present in myelin using both Western blotting and the highly specific ADP ribosylation of rho proteins in the presence of Clostridium botulinum C3 and Limosum toxins. Attempts to isolate the rho protein for sequence analysis proved difficult, as quantities in myelin are small. Some of the rho group of GTPases are found in the cytoskeletal fraction of CNS myelin, which is believed to be rich in the radial element. The association appears inhibited by ADP ribosylation (inactivation).Further study of both the proteins and genes of CNS myelin is indicated if understanding of the processes of de- and remyelination are to be understood in the healthy state and in diseases such as multiple sclerosis.</p