To analyze the genes related to the pathophysiology of sporadic amyotrophic lateral sclerosis (SALS) we performed gene profiling of SALS spinal cords using molecular indexing combined with cDNA microarray. Eighty-four fragments were cloned in the first screening procedure with molecular indexing. Subsequent quantitative microarray screening revealed 11 genes which were differentially expressed in SALS. Real-time RT-PCR verified that the expression level of the following six genes was altered in SALS: dorfin, metallothionein-3, 30 kDa TATA-binding protein-associated factor, neugrin, ubiquitin-like protein 5 and macrophage-inhibiting factor-related protein-8. These results indicated that genes associated with the ubiquitin-proteasome system, oxidative toxicity, transcription, neuronal differentiation and inflammation might be involved in the pathogenesis of SALS.