Recombinant Human NOTCH3 protein

NOTCH3 is a member of the Notch receptor family, evolutionarily conserved transmembrane proteins critical for cell-cell communication and regulation of cellular processes like differentiation, proliferation, and apoptosis. Structurally, NOTCH3 consists of an extracellular domain with epidermal growth factor (EGF)-like repeats, a transmembrane region, and an intracellular domain. It is predominantly expressed in vascular smooth muscle cells and pericytes, playing a vital role in maintaining vascular homeostasis and arterial development.

Mutations in the NOTCH3 gene are linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary small-vessel disease characterized by recurrent strokes, vascular dementia, and migraine. These mutations typically occur within the EGF-like repeats, disrupting protein folding, receptor signaling, or leading to toxic accumulation of extracellular aggregates. Studying NOTCH3's molecular mechanisms is essential for understanding CADASIL pathogenesis and developing targeted therapies.

Recombinant NOTCH3 proteins are engineered in vitro using expression systems (e.g., mammalian, insect cells) to produce functional or domain-specific variants for research. These proteins retain key structural motifs, enabling studies on ligand-receptor interactions (e.g., with Delta/Serrate/LAG-2 ligands), signaling pathways, and mutation-induced dysfunction. Researchers utilize recombinant NOTCH3 to model disease mechanisms, screen therapeutic compounds, or engineer biologics to modulate Notch signaling. Its applications extend to vascular biology, neurodegenerative disease research, and regenerative medicine, offering insights into how disrupted Notch signaling contributes to vascular degeneration and neurological deficits. Such tools are pivotal for advancing diagnostics and treatments for CADASIL and related vascular disorders.