What is Neuronal Specific Enolase (NSE)?

What is Neuron-specific enolase (NSE)?

Neuron-specific enolase (NSE) is an enzyme specific to neurons and neuroendocrine cells. As a sensitive indicator for evaluating the severity of nerve cell damage and predicting prognosis, NSE is widely used in various nerve injuries such as cerebral hemorrhage, ischemia, hypoxia, infection, poisoning, malnutrition, etc. Meanwhile, due to the high content of NSE in neuroendocrine cells, it is also often used for the diagnosis and prognosis evaluation of small-cell lung cancer.

Neuron-specific enolase NSE is widely used in clinical and experimental evaluation of the severity of brain injury and the prognosis of the disease. It has been taken seriously by scientists and medical personnel, and its molecular structure has been measured and classified, its various subtypes have been identified, and further differences in distribution and distribution patterns in different tissues have been calculated.

Because of the high content of NSE in nervous tissue, it is used in clinical monitoring of changes in the condition of brain injuries caused by various reasons, and overall assessment of patients' prognosis. Meanwhile, due to the high content of NSE in neuroendocrine cells, it is also widely used for the diagnosis and prognosis evaluation of small-cell lung cancer.

Development of neuron-specific enolase (NSE)

In 1965, scientist Moore first discovered an acidic soluble protein widely distributed in the nervous tissue of the brain and of almost no existence in non-nervous tissues, called 14-3-2 protein, namely NSE.

In subsequent studies, it was found that NSE is one of the gene superfamily members of enolase, and NSE has enolase activity, which can catalyze the cleavage of α-phosphoglycerate to generate phosphoenolpyruvate. This is an important step for the production of energy in aerobic and anaerobic glycolysis, which is of great significance for the smooth progress of sugar metabolism and ATP generation in the body.

Enolase is mainly composed of three subunits, namely α, β, and γ. Currently, five isozymes of it are known, namely αα, ββ, γγ, αβ, and αγ. The α subunit is called non-neuronal enolase (NNE) because the α subunit is mainly distributed in tissues such as the liver and kidney; The β subunit is called muscle-specific enolase (MSE) because the β subunit is mainly distributed in skeletal and cardiac muscles; while the γ subunit mainly exists in nervous tissue, which is divided into two isozymes specific to neurons and neuroendocrine cells, respectively γγ and αγ. Therefore, they are named NSE.

The biological half-life of NSE may be greater than 20 hours, with a molecular weight of 78 kD and an isoelectric point of pH 4.7. It is an acidic proteinase. The full length of the NSE gene nucleotide sequence is 2423 bp, encoding 434 amino acid residues.

The three-dimensional structure of the γ subunit of NSE includes an N-terminal region of about 130 amino acids, and eight α-helical-β-folded barrel structures composed of about 300 amino acids, in which the β-folded structure is located in the core of the barrel structure. The β-folded structure is the catalytic center of NSE, and the α-helical structure surrounds the cylindrical structure.

The catalytic center of NSE is mainly composed of three basic amino acids, histidine-189, arginine-371, and lysine-393. All of the antigenic determinants of NSE are distributed in the 48-96, 188-293, and 399-433 amino acid sequence regions, which can be used for NSE detection.

The spatial structure of the human NSE dimer complex is asymmetric, with one subunit containing a sulfate ion and two magnesium ions, and its conformation is closed. It is found that this subunit can bind to the substrate or its analog. On the other hand, no spatial conformation of the other subunit binding to any substrate or analog has been found, indicating negative cooperativity between different subunits after binding to the ligand.

NSE is a large molecular protein that is present in very low amounts in normal peripheral fluids. It is most widely distributed in brain tissue and accounts for 1.5%-3.0% of all soluble proteins in the brain nerve tissue. It accounts for 40%-65% of enolase in the human brain cortex. The gray matter contains a large number of neurons, so its NSE content is high. The NSE content of peripheral nerves is only 1%-10% of that in the central nervous system. Therefore, NSE in gray matter is the highest, followed by spinal cord and peripheral ganglia.

A certain amount of γ subunit is also present in the cells of tissues with neuroendocrine function, such as the pituitary, pineal, and thyroid, accounting for 2.0%-3.3% of the brain nerve tissue. Therefore, NSE can be used as a characteristic biomarker of nerve injury.