A 14-3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord

We have recently isolated a 2.2-kb cDNA clone (1C5) from a human spinal cor d cDNA library with partial identity to the 14-3-3 protein mRNA encoding th e a protein (YWHAQ). 14-3-3 protein transcripts are highly expressed in lar ge projection neurones of the hippocampus, cerebellum, and spinal cord and have been found to be significantly up-regulated in rat motor neurones foll owing hypoglossal nerve axotomy. In this study we investigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord was involved in amyotrophi c lateral sclerosis (ALS). We found a significant up-regulation of 1C5 (YWH AQ) in lumbar spinal cord from patients with sporadic ALS compared with con trols, with the highest levels of expression being found in individuals wit h predominant lower motor neurone involvement. A 6-bp tandem repeat in the 5'-untranslated region of the gene was found to be polymorphic, but no sign ificant association with disease was found following genomic analysis of th is region. The localisation of 1C5 (YWHAQ) to chromosome 2 was determined a nd coincides with that reported for clone HS1 (EMBL accession no. X57347), These results show the marked up-regulation of the 14-3-3 isoform (YWHAQ) i n ALS spinal cord and indicate the involvement of a potential 14-3-3-mediat ed survival pathway in the pathogenesis of ALS.