Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis

Clinical Proteomics

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

[1] Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India;Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India;Department of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, IndiaDepartment of Neurology, National Institute of Mental Health and Neuro Sciences, Bangalore, India;Institute of Bioinformatics, Bangalore, IndiaInstitute of Bioinformatics, Bangalore, IndiaInstitute of Bioinformatics, Bangalore, India

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

DOI  :  10.1186/1559-0275-10-19

来源: Humana Press Inc

【 摘 要 】

Abstract

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】

Unknown