Related Experiment Videos
A 14-3-3 mRNA is up-regulated in amyotrophic lateral sclerosis spinal cord
A Malaspina1, N Kaushik, J de Belleroche
1Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, London, England.
Abstract:
We have recently isolated a 2.2-kb cDNA clone (1C5) from a human spinal cord cDNA library with partial identity to the 14-3-3 protein mRNA encoding the theta protein (YWHAQ). 14-3-3 protein transcripts are highly expressed in large projection neurones of the hippocampus, cerebellum, and spinal cord and have been found to be significantly up-regulated in rat motor neurones following hypoglossal nerve axotomy. In this study we investigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord was involved in amyotrophic lateral sclerosis (ALS). We found a significant up-regulation of 1C5 (YWHAQ) in lumbar spinal cord from patients with sporadic ALS compared with controls, with the highest levels of expression being found in individuals with 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 significant association with disease was found following genomic analysis of this region. The localisation of 1C5 (YWHAQ) to chromosome 2 was determined and 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) in ALS spinal cord and indicate the involvement of a potential 14-3-3-mediated survival pathway in the pathogenesis of ALS.
Insights
This study found increased levels of the 14-3-3 theta protein (YWHAQ) in the spinal cords of amyotrophic lateral sclerosis (ALS) patients. This suggests a potential role for 14-3-3 proteins in ALS pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- 14-3-3 proteins are crucial for neuronal function and survival.
- 14-3-3 transcripts are highly expressed in projection neurons and up-regulated in motor neurons after injury.
- The specific isoform YWHAQ (1C5 transcript) was investigated for its role in amyotrophic lateral sclerosis (ALS).
Purpose of the Study:
- To investigate the involvement of the 1C5 transcript (YWHAQ) in amyotrophic lateral sclerosis (ALS).
- To determine the expression levels of YWHAQ in spinal cord samples from ALS patients and controls.
- To explore the potential role of 14-3-3 mediated pathways in ALS pathogenesis.
Main Methods:
- Isolated a 2.2-kb cDNA clone (1C5) from a human spinal cord library.
- Analyzed YWHAQ expression in lumbar spinal cord tissue from sporadic ALS patients and controls.
- Performed genomic analysis of a polymorphic 6-bp tandem repeat in the 5'-untranslated region.
- Determined the chromosomal localization of the 1C5 (YWHAQ) gene.
Main Results:
- Significant up-regulation of 1C5 (YWHAQ) was observed in the lumbar spinal cord of sporadic ALS patients compared to controls.
- Highest YWHAQ expression levels were found in ALS patients with predominant lower motor neuron involvement.
- A 6-bp tandem repeat in the 5'-untranslated region was polymorphic, but showed no significant association with ALS.
- The 1C5 (YWHAQ) gene was localized to chromosome 2.
Conclusions:
- The 14-3-3 theta isoform (YWHAQ) is markedly up-regulated in the spinal cord of ALS patients.
- These findings suggest a potential 14-3-3-mediated survival pathway involved in the pathogenesis of ALS.
- YWHAQ may play a role in the neuronal degeneration observed in ALS, particularly affecting lower motor neurons.