Proteomic analysis of the cerebrospinal fluid from patients with amyotrophic lateral sclerosis based on tandem mass spectrometry technique

Abstract

To investigate the differentially expressed proteins in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS) at the proteomics level using tandem mass spectrometry label (TMT) technique and explore the pathogenic mechanism and related pathways of ALS. Between November, 2017 and April, 2018, 5 patients with medulla oblongata onset ALS and 5 patients with limb onset ALS were selected from the Departments of Neurology of 928 Hospital of Army Joint Logistics Support Force of PLA and Xiangya Hospital of Central South University, with 5 patients with migraine and low intracranial pressure headache serving as the healthy controls.CSF samples were obtained from all the participants, and the differentially expressed proteins in the CSF were identified using tandem mass spectrometry (TMT) technique with bioinformatics analysis. A total of 1530 proteins were identified and quantified in the CSF samples.The expression of 48 proteins was up-regulated and 6 proteins were down-regulated in medulla oblongata onset ALS patients; 16 proteins were up-regulated and 19 were down-regulated in limb onset ALS patients.GO analysis showed that these proteins, which were distributed both within and outside the cells, were involved in cell physiological process, single organ process and biological regulation and had binding function, catalytic activity, and receptor activity.KEGG pathway analysis showed that the up-regulated proteins in the CSF from patients with medulla oblongata onset ALS participated in 3 pathways involving the lysosomes, metabolism, and measles.The down-regulated proteins in the CSF from patients with limb onset ALS participated in 7 pathways involving the complement and coagulation cascade, Staphylococcus aureus infection and herpes simplex infection, and all the pathways contained complement components. The CSF samples of ALS patients with medullary onset and limb onset have differentially expressed proteins.The lysosomal pathway is involved in the occurrence and progression of ALS with medullary onset, and the immune responses are involved in the occurrence and progression of ALS with limb onset.