Investigations of neurofilament and macrophage migration inhibitory factor protein levels in ALS patients

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with adult onset. Progressive degeneration of upper motor neurons in the motor cortex and lower motor neurons in the spinal cord and brain stem cause voluntary muscle atrophy. It is suggested that the incidence of the disease is 4-8 / 100,000 / year and the prevalence is 3-8 / 100,000. Onset of ALS can be in extremities, bulbar region or trunk. In the later stages of ALS disease, death occurs because of the failure of respiratory muscles. The etiology of ALS is not fully understood, but mechanisms such as genetic factors, oxidative stress, abnormalities of RNA mechanisms, endoplasmic reticulum stress, neuroinflammation and protein aggregations are thought to play roles in the development of the disease. Diagnosis of ALS disease is difficult, because of absence of specific diagnostic test. Biomarkers are molecules that are indicative of changes in biochemical pathways during disease. Biomarkers are used to monitor the diagnosis and prognosis of the disease. They are also important in the process of drug development and identification of new drug targets. One group of the candidate biomarkers for ALS are neurofilaments. Neurofilaments are important components of neurons-specific cytoskeleton and are involved in the formation of the axon structure. Neuroinflammation is also a mechanism that plays a role in the development of ALS. It is known that changes in the level of neuroinflammation and molecules related to the immune system have occured during ALS disease. One of these molecules is the macrophage migration inhibitory factor, which is briefly referred to as MIF. The MIF is a cytokine-like molecule that allows the formation of an immunologic response. It also acts as an enzyme to intervene in some cellular events. In this study, it was aimed to investigate the differences between the phospfoneurofilament heavy chain and MIF proteins as biomarker candidates among ALS patients, healthy control and neurological control groups. For this purpose, the plasma fraction was obtained from blood taken from patients and controls. ELISA sandwich method was used to measure protein levels in the plasma. The obtained data were analyzed by SPSS 23.0 program. The level of phosphoneurofilament heavy chain protein was found to be statistically different in ALS patient group compared to healthy control group (p <0.05). The level of this protein was found to be higher in the ALS patient group. In addition, the level of MIF protein was statistically different in the ALS group compared to the healthy control group (p <0.05). It was observed that the level of MIF protein was higher in the ALS patient group than in the control group. As a result of the correlation analysis, it was found that there was a strong positive correlation between phosphoneurofilament protein and MIF protein levels (p <0.01). As a result; the levels of these proteins are higher in the ALS patient group than in the healthy control group. In the study, the neurological control group consisted of a heterogeneous group of patients. There was no statistically significant difference between levels of MIF and phosphoneurofilament protein among this patient group and ALS patient group. Keywords: Phosphoneurofilament, pNFH, MIF, Macrophage Migration Inhibitor Factor, ELISA, ALS