Modulating the blood-brain barrier in CNS disorders: A review of the therapeutic implications of secreted protein acidic and rich in cysteine (SPARC).

Secreted protein acidic and rich in cysteine (SPARC), an essential stromal cell protein, plays a crucial role in angiogenesis and maintaining endothelial barrier function. This protein is expressed by diverse cell types, including endothelial cells, fibroblasts, and macrophages, with increased expression found in regions of tissues undergoing active remodeling, repair, and proliferation. The role of SPARC in non-neural tissues is of significant interest. In the central nervous system (CNS), SPARC is highly expressed in blood vessels during early development. It becomes down-regulated as the brain matures, a pattern consistent with its role in angiogenesis and blood-brain barrier (BBB) establishment. In this review, we explore the multifaceted roles of SPARC in regulating CNS disorders, particularly its action in angiogenesis, inflammatory responses, neural system development and repair, barrier establishment, maintenance of BBB function, and the pathogenesis of CNS disorders triggered by BBB dysfunction.