ENO2

Gamma enolase is a dimeric protein consisting of 433 amino acid residues and having two isoforms γγ and αγ; gamma enolase is also called neurospecific ^[1] .

The molecular weight of the subunits is 39 kDa, the full form weighs about 78 kDa depending on the subunit composition ^[2] .

It is localized in neurons, cells of neuroendocrine origin (chromaffin cells of the brain, parafollicular cells of the thyroid gland, and others). The level of NSE increases with diseases of the nervous system, accompanied by a fairly rapid destruction of neurons, therefore, it is used in the diagnosis and assessment of the prognosis of recovery in lesions of the nervous system of various origins (traumatic, ischemic) ^[1] . The γγ isoform predominantly occurs in mature neurons and is used as a marker of neuronal maturation and differentiation, while the αγ isoform is more located in cells of non-neuronal origin ^[3] .

The catalytic activity of enolase requires the natural cofactor Mg² +. Two types of metal binding sites favor catalysis. Site I is called "conformational", so it causes conformational changes and provides binding to the substrate or substrate analogs. The divalent metal ion binds to the “catalytic” site II and provides a catalytic reaction ^[4] .

Human NSE is one of the main proteins of the brain, which makes up from 0.4% to 2.2% of the total volume of soluble protein in it, depending on the region. In some regions, NSE makes up 3-4% of the total soluble protein, which led to the general use of NSE as a clinical marker of neuronal and neuroendocrine cells ^[4] .

It is well known that glycolysis increases dramatically in tumor cells and is a hallmark of cancer progression. In tumors, the lack of circulation of nutrients and oxygen leads to the predominance of anaerobic glycolysis over mitochondrial oxidative phosphorylation. This metabolic switch is also called the Warburg effect, which allows tumor cells to receive energy regardless of the presence of oxygen ^[5] .

Malignant transformation of astrocytic, thoracic, and urogenital cells leads to an increase in gamma enolase, which is their way of adapting to increase metabolic needs ^[6] .

Also, the level of gamma enolase increases in stressful situations, this is shown on glioblastoma cells subjected to hypoxia and serum starvation. The glycolytic function of gamma enolase and its effect on stimulating the growth of tumor cells is a promising target for cancer therapy ^[7] .

An important condition for cell migration is the dynamic remodeling of cytoskeleton actin. Redevelopment is stimulated by several molecules that link the migration signal to actin and positively regulate invasive and metastatic cancer cells. Gamma enolase, by interacting with actin filaments and regulating the function of the RhoA kinase, is involved in the migration of tumor cells. ^[one]