The synucleins are a small, soluble, highly conserved group of neuronal proteins that have been implicated in neurodegenerative diseases and cancer. The synuclein family consists of α-, β-, and γ-synuclein (SNCG). Synuclein-γ (SNCG) is a human gene localized at 10q23.20–23.3. SNCG cDNA is ~5 kb in length and comprised of five exons that are translated into a protein of 127 amino acids. In cooperation with other members of the family, γ-synuclein plays role in regulation of dopaminergic neurotransmission. Changes of γ-synuclein expression in peripheral tissues has been linked with metabolic and oncological diseases. SNCG is not clearly involved in neurodegenerative diseases. However, a stage-specific upregulation of SNCG has been found in advanced breast carcinomas and other malignancies, including ovarian, gastric, esophagus, liver, colon, pancreatic, and bladder cancers. γ-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Midkine (MK, also called neurite growth promoting factor 2, NEGF-2), a product of a retinoic acid responsive gene, is a secreted 13 kDa protein belonging to the family of heparin binding growth/differentiation factors. Midkine is composed of two domains held together by disulfide linkages. The C-terminally located domain contains two heparin binding sites and is usually responsible for midkine activity. Part of the MK activity is enhanced by dimerization of MK. Midkine has been found in vertebrates from human to zebrafish and is most strongly expressed in midgestation. In the adult MK expression is restricted. In addition to normal development, MK is also involved in the pathogenesis of diseases, e.g. inflammatory diseases, human carcinomas such as esophageal, stomach, colon, pancreatic, thyroid, lung, urinary, hepatocellular, neuroblastoma, glioblastoma, Wilm´s tumor etc. High MK levels are associated with poor prognosis in some types of cancer. The increased expression in many carcinomas indicates that MK can be applied to the diagnosis of malignancy. Midkine is expressed during the reparative stage of bone fractures, also supresses infection of cells by some viruses including HIV. Anti-apoptotic and cell protecting activity of midkine makes it promising in therapy. Clinical use and areas of investigation: - Bladder cancer - Oncology - Inflammatory diseases - Preservation and repair of injured tissues
- References to Bladder Cancer Panel