Syncytin-A (SynA)

Syncytin-A is a murine endogenous retroviral (ERV) envelope protein encoded by the Syna gene, which has been evolutionary co-opted to perform essential functions in placental development. It is a highly fusogenic membrane glycoprotein that mediates the fusion of trophoblast cells to form the syncytiotrophoblast layer, a critical structure for nutrient exchange and fetal-maternal tolerance. While Syncytin-A is specific to rodents, it is functionally analogous to human Syncytin-1 (encoded by ERVW-1). In humans, the dysregulation of syncytin proteins is implicated in various pathologies, including preeclampsia, where reduced expression leads to placental defects, and multiple sclerosis, where the HERV-W envelope protein (Syncytin-1) acts as a pro-inflammatory neurotoxin. Therapeutic development has focused on the human counterpart, with the monoclonal antibody temelimab (GNbAC1) designed to neutralize the HERV-W envelope protein to treat neurodegenerative diseases. Syncytin-A interacts with its specific receptor, Ly6e, to trigger membrane fusion, whereas its human counterpart utilizes the ASCT2 (SLC1A5) transporter.

Other names

SynaEnvelope glycoprotein syncytin-AMurine syncytin-A

Temelimab (formerly GNbAC1) is a recombinant humanized monoclonal antibody that targets and neutralizes the human HERV-W envelope protein (Syncytin-1), which is the functional analog of Syncytin-A. It blocks the pro-inflammatory and neurotoxic effects of the protein, particularly its interaction with Toll-like receptor 4 (TLR4) on immune cells, to mitigate neurodegeneration in diseases like multiple sclerosis.