Summary of `Superoxide Dismutase (SOD) and Free Radicals in Amyotrophic Lateral Sclerosis and Neurodegeneration' conference

Abstract

An international symposium entitled ``Superoxide Dismutase (SOD) and Free Radicals in Amyotrophic Lateral Sclerosis and Neurodegeneration'' was held at the Harrison Conference Center in Lake Bluff, IL, September 9 to 11, 1994. This symposium was planned as a result of the recent identification of mutations in the Cu,Zn SOD gene, SOD-1, in familial amyotrophic lateral sclerosis (FALS). The conference brought together experts on the biochemistry, structure, and function of SOD along with neuroscientists and neurologists to discuss the mechanisms by which SOD mutation leads to motor neuron (MN) death, the relationship of free radical damage to FALS and non-FALS neurodegenerative diseases, and therapeutic approaches in FALS. The 37 invited speakers were joined by an additional 87 registered attendees. Siddique (Northwestern University, Chicago, IL) and Brown (Harvard Medical School, Boston, MA) reported that approximately 20% of cases of FALS are linked to chromosome 21, and these are associated with more than 20 different mutations in SOD-1. A number of other investigators extended the list of specific SOD-1 mutations associated with FALS (Aoki, Tohoku University, Sendai, Japan; Laing, Queen Elizabeth II Medical Center, Nedlands, West Australia; Tsuji, Niigata University, Niigata, Japan). The association of particular mutations with the duration of disease was noted (eg, exon 1 mutations are associated with a more rapidly progressive disease). Further genetic studies may identify additional mutations or polymorphisms that influence other aspects of disease, such as age at onset (Pericak-Vance, Duke University, Durham, NC). Further confirmation of the importance of SOD-1 mutations in the pathogenesis of FALS was provided by transgenic mouse studies (Gurney, Northwestern University, Chicago, IL; Gordon, Mt. Sinai Medical Center, New York, NY; Price, Johns Hopkins University, Baltimore, MD). The latter studies demonstrated that the presence of different FALS SOD-1 mutations as transgenes leads to MN degeneration. The pathology includes a remarkable vacuolation …