A 14-3-3 mRNA Is Up-Regulated in Amyotrophic Lateral Sclerosis Spinal Cord


  • Andrea Malaspina,

  • Narendra Kaushik,

  • Jackie de Belleroche

  • Lippincott Williams & Wilkins, Inc., Philadelphia

  • Dr. A. Malaspina and Dr. N. Kaushik contributed equally to thisresearch.

  • Abbreviations used: ASK 1, apoptosis signal-regulating kinase 1;ALS, amyotrophic lateral sclerosis; Erk, extracellular signal-regulatedkinase; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; PD, Parkinson'sdisease; PKC, protein kinase C; SDS, sodium dodecyl sulphate; SOD1,copper/zinc-dependent superoxide dismutase; SSC, saline—sodium citrate;TNRT, trinucleotide/tandem repeat-containing transcript; TR, tandem repeat;UTR, untranslated region.

Address correspondence and reprint requests to Prof. J. de Belleroche atDepartment of Neuromuscular Diseases, Division of Neuroscience andPsychological Medicine, Imperial College School of Medicine, Fulham PalaceRoad, London W6 8RF, U.K. E-mail:j.belleroche@ic.ac.uk


Abstract: We have recently isolated a 2.2-kb cDNA clone (1C5) from ahuman spinal cord cDNA library with partial identity to the 14-3-3 proteinmRNA encoding the θ protein (YWHAQ). 14-3-3 protein transcripts arehighly expressed in large projection neurones of the hippocampus, cerebellum,and spinal cord and have been found to be significantly up-regulated in ratmotor neurones following hypoglossal nerve axotomy. In this study weinvestigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord wasinvolved in amyotrophic lateral sclerosis (ALS). We found a significantup-regulation of 1C5 (YWHAQ) in lumbar spinal cord from patients with sporadicALS compared with controls, with the highest levels of expression being foundin individuals with predominant lower motor neurone involvement. A 6-bp tandemrepeat in the 5′-untranslated region of the gene was found to bepolymorphic, but no significant association with disease was found followinggenomic analysis of this region. The localisation of 1C5 (YWHAQ) to chromosome2 was determined and coincides with that reported for clone HS1 (EMBLaccession no. X57347). These results show the marked up-regulation of the14-3-3 isoform (YWHAQ) in ALS spinal cord and indicate the involvement of apotential 14-3-3-mediated survival pathway in the pathogenesis of ALS.