Modulators of cystein proteases and cell-death markers in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective damage of motor neurons in the brain and spinal cord. The aim of the current study was to reveal new specific markers of neurodegeneration in the cerebrospinal fluid (CSF) of ALS patients. We measured the activities of substances that modulate the activity of cysteine proteases (calpain, caspase, and cathepsin B) in the CSF of ALS patients. The CSF of ALS patients, in contrast to the CSF of patients with multiple sclerosis, inhibits calpain and cathepsin B significantly more strongly, as compared to the control CSF. The LDH activity and the concentration of neuron-specific enolase (NSE) in the CSF of control patients and ALS patients did not differ. The concentration of neurofilament heavy chains in the CSF was significantly higher in the ALS patients as compared to the control group. The albumin index increased in 50% of all ALS patients. We also have shown a correlation between the cathepsin inhibitor activity, the concentration of neurofilament heavy chains, and the albumin index and the clinical findings of the disease. According to our data, the concentration of neurofilament heavy chains is a sensitive marker of neurodegenerative process during ALS. An increase in the CSF inhibiting activity with respect to cathepsin B and calpain is specific for ALS and may confirm the role of an imbalance of proteolytic systems in the pathogenesis of this disease.