Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

Clinical Proteomics

Trichur R Raju²  Phalguni Anand Alladi²  Atchayaram Nalini³  Srinivas MM Bharath¹  Talakad N Sathyaprabha²  Hindalahalli Chandregowda Harsha⁴  Kalyan Vijayalakshmi²  Poojashree Mishra²  Aparna Sharma²  Anu Mary Varghese² 

[1] Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore 560 029, India;Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Post Box no.: 2900, Bangalore 560 029, India;Department of Neurology, National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore 560 029, India;Institute of Bioinformatics, Discoverer Building, International Tech Park, Whitefield, Bangalore 560 066, India

关键词: Sporadic amyotrophic lateral sclerosis;    Cerebrospinal fluid;    Proteomics;   

Others  :  803410
DOI  :  10.1186/1559-0275-10-19

 received in 2013-07-27, accepted in 2013-11-18,  发布年份 2013

【 摘 要 】

Background

Potential biomarkers to aid diagnosis and therapy need to be identified for Amyotrophic Lateral Sclerosis, a progressive motor neuronal degenerative disorder. The present study was designed to identify the factor(s) which are differentially expressed in the cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (SALS; ALS-CSF), and could be associated with the pathogenesis of this disease.

Results

Quantitative mass spectrometry of ALS-CSF and control-CSF (from orthopaedic surgical patients undergoing spinal anaesthesia) samples showed upregulation of 31 proteins in the ALS-CSF, amongst which a ten-fold increase in the levels of chitotriosidase-1 (CHIT-1) was seen compared to the controls. A seventeen-fold increase in the CHIT-1 levels was detected by ELISA, while a ten-fold elevated enzyme activity was also observed. Both these results confirmed the finding of LC-MS/MS. CHIT-1 was found to be expressed by the Iba-1 immunopositive microglia.

Conclusion

Elevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS.

【 授权许可】

   
2013 Varghese et al.; licensee BioMed Central Ltd.

【 图 表 】

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