Syndecan-3 (SDC3) is a member of the syndecan family of cell-surface molecules. It has diverse biological roles, being involved in processes like cell-cell and cell-matrix interactions, and is associated with multiple signaling pathways. SDC3 has been implicated in the normal growth and development, with its null mice growing and developing normally but showing subtle anatomical phenotypes in the brain [2].

In the context of neurodegenerative diseases, knockdown of SDC3 attenuated oxidative stress-induced cell death in SN56-APPSWE cells, suggesting that SDC3 mediates the specific effect of the APPSWE mutation on cholinergic neurodegeneration in Alzheimer's disease (AD). This indicates a potential role of SDC3 in AD pathogenesis and implies it could be a target to alleviate selective neurodegeneration in AD [1]. In apparent treatment-resistant hypertension (aTRH), a genome-wide association study found an association between SDC3 and aTRH, with lower SDC3 expression in aTRH patients, contributing to the understanding of aTRH etiopathogenesis and potentially serving as a therapeutic target [3].

In summary, SDC3 is involved in various biological processes including normal development, neurodegeneration, and hypertension-related mechanisms. The use of gene knockout models like SDC3 null mice has provided insights into its functions in normal development, while knockdown experiments in disease-relevant cell models have revealed its potential roles in AD and aTRH, highlighting its importance as a possible therapeutic target in these disease areas.

References:

1. Wang, Juelu, Chen, Peiye, Hu, Bolang, Wu, Yili, Song, Weihong. . Distinct effects of SDC3 and FGFRL1 on selective neurodegeneration in AD and PD. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e22773. doi:10.1096/fj.202201359R. https://pubmed.ncbi.nlm.nih.gov/36629784/

2. Arokiasamy, Samantha, Balderstone, Michaela J M, De Rossi, Giulia, Whiteford, James R. 2020. Syndecan-3 in Inflammation and Angiogenesis. In Frontiers in immunology, 10, 3031. doi:10.3389/fimmu.2019.03031. https://pubmed.ncbi.nlm.nih.gov/31998313/

3. Xiao, Xiao, Li, Rui, Wu, Cunjin, Hui, Rutai, Wang, Yibo. 2022. A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension. In BMC medicine, 20, 463. doi:10.1186/s12916-022-02665-x. https://pubmed.ncbi.nlm.nih.gov/36447229/