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Published on: January 12, 2015
Abnormal expression of truncated CRMP-1 protein in the brain cortex of MPSIIIB mice
David Cheillan1, Céline Malleval, Jérôme Ausseil
1INSERM, U842, Université de Lyon, Lyon1, UMR-S842, Faculté de Médecine Laennec, Lyon F-69372, France. david.cheillan@chu-lyon.fr
Abstract:
Mucopolysaccharidosis IIIB is a lysosomal disease characterized by a severe neurological deterioration, the pathophysiological mechanisms of which are poorly understood. Recently FGF pathway was shown to be altered leading us to explore a downstream target involved in brain development: the collapsin response mediator protein-1 (CRMP-1). CRMP-1 transcript level was normal but a cleavage of CRMP-1 was observed with an abnormal expression of the truncated form until adult age. This truncated CRMP-1 protein could play a role in post-natal cortex maturation and be involved in neuronal alterations occurring in lysosomal diseases.
Insights
Mucopolysaccharidosis IIIB involves altered collapsin response mediator protein-1 (CRMP-1) expression, specifically a truncated form. This finding may explain neuronal changes in lysosomal diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Mucopolysaccharidosis IIIB (MPS IIIB) is a lysosomal storage disease causing severe neurological decline.
- The underlying mechanisms of MPS IIIB neurological deterioration remain largely unknown.
- Recent studies indicate alterations in the Fibroblast Growth Factor (FGF) signaling pathway in MPS IIIB.
Purpose of the Study:
- To investigate the role of collapsin response mediator protein-1 (CRMP-1), a downstream FGF target, in MPS IIIB.
- To examine CRMP-1 expression and potential alterations in MPS IIIB pathophysiology.
- To understand CRMP-1's involvement in brain development and neuronal dysfunction in lysosomal diseases.
Main Methods:
- Analysis of CRMP-1 transcript levels in affected individuals.
- Detection and characterization of CRMP-1 protein expression, including truncated forms.
- Correlation of CRMP-1 expression patterns with disease progression and age.
Main Results:
- CRMP-1 transcript levels were found to be normal in MPS IIIB.
- A significant cleavage of CRMP-1 was observed, leading to abnormal expression of a truncated protein.
- This truncated CRMP-1 form persisted until adulthood in individuals with MPS IIIB.
Conclusions:
- The abnormal expression of truncated CRMP-1 may contribute to post-natal cortex maturation defects.
- Altered CRMP-1 processing is implicated in the neuronal alterations observed in lysosomal diseases like MPS IIIB.
- CRMP-1 represents a potential therapeutic target for mitigating neurological damage in MPS IIIB.
