Anti-SNCG: Mouse γ-Synuclein Antibody

BACKGROUND Synuclein-gamma (SNCG) is a highly conserved 127-amino acid 13 kD cytoplasmic protein and a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. SNCG is expressed in the peripheral nervous system, mainly in primary sensory neurons, sympathetic neurons, and motor neurons. It was also detected in heart, skeletal muscle, ovary, testis, colon, spleen, pancreas, kidney and lung. Moreover, high levels of SNCG have been identified in advanced breast carcinomas suggesting a correlation between overexpression of SNCG and breast tumor development. Thus, it was also called breast cancer-specific protein 1(BCSG1). SNCG was also detected in ovarian tumors, and in the olfactory epithelium.¹

Synuclein-gamma is similar to the amyloid protein nonamyloid beta fragment and to alpha-synuclein and beta-synuclein. The synuclein proteins contain several repeated domains that display variations of a KTKEGV consensus sequence. This motif, repeated six to seven times in the amino-terminal portion of the protein, is reminiscent of the alpha-helical domains of the apolipoproteins and suggests lipid binding properties. The normal cellular function of Synuclein-gamma is as yet unknown, but interestingly exogenous expression of the protein increases the invasive and metastatic potential of breast tumors. The highly conserved N-terminal region is known to be important for the lipid interactions of the synucleins and the highly acidic C-terminal region has been suggested to possess chaperone-like activity, to regulate the aggregation of synucleins and to mediate protein¬protein interactions. It seems that gamma-synuclein plays a role in neurofilament network integrity and may modulate axonal architecture, also, it may increase the susceptibility of neurofilament-H to calcium-dependent proteases and may also modulate the keratin network in skin. Phosphorylation by GRK5 appears to occur on residues distinct from other kinase target residues. Synuclein gamma is likely involved in the pathogenesis of neurodegenerative diseases and SNCG is expressed at very high level in advanced infiltrating breast cancer. Sequence analysis suggests that the protein from tumour cells (BCSG1) is different from the protein expressed in the nervous system. Substitution of two lysines by glutamates in BCSG1 changes the overall charge of the persyn molecule and disturbs EKTKEGV repeats that are highly conserved in the synuclein family. Such changes should have serious consequences for protein structure and function. The dual role of SNCG in neurodegeneration and malignancy could involve common mechanisms. Changes in organization of the cell cytoskeleton are among the most prominent characteristics of both processes. The involvement of Synuclein-gamma in regulating neurofilament network integrity raises the possibility that it may also affect the intermediate filament network in malignant breast epithelial cells. It was shown recently that Synuclein-gamma may promote cancer progression by suppressing endoplasmic reticulum stress-induced apoptosis.² In addition the molecular targets of SNCG during breast cancer progression may include estrogen receptor (ER)-α36, a Variant of ER-α. It was demonstrated that SNCG can replace the function of heat shock protein 90, chaperone ER-α36 activity, stimulate ligand-dependent cell growth, and render tamoxifen resistance.³ Moreover, SNCG is closely realated with many other cancers. It was shown that synuclein-gamma is closely involved in perineural invasion/distant metastasis and is a significant prognostic factor in pancreatic cancer. Synuclein-γ may serve as a promising molecular target of early diagnosis and anticancer therapy.⁴
 

REFERENCES  

1. Jiang, Y. et al: Cancer Res. 64:4539-46, 2004
2. Hua, H. et al: J. Pathol. 217:507-15, 2009
3. Shi, Y.E. et al: Am. J. Pathol. 177:964-73, 2010
4. Hibi, T. et al: Clin. Cancer Res. 15:2864-71, 2009