NCSTN Protein is a protein encoded by the NCSTN gene that nicastrin functions as part of the gamma-secretase complex which includes:. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [1]
Nicastrin (NCSTN) is a essential component of the gamma-secretase complex, a membrane-bound protease that catalyzes the final cleavage of amyloid precursor protein (APP) to produce amyloid-beta peptides. Nicastrin acts as the substrate-recognition subunit of the complex and is a key therapeutic target for Alzheimer's disease. [2]
Nicastrin is a large type I transmembrane glycoprotein: [3]
| Property | Value | [4]
|----------|-------|
| Gene | NCSTN |
| UniProt | Q9Y5G0 |
| Molecular Weight | ~230 kDa |
| Subcellular Localization | Endoplasmic reticulum, Golgi, plasma membrane |
| Protein Family | Anterior pharynx defective (APH) family |
Nicastrin functions as part of the gamma-secretase complex which includes:
The complex cleaves type I transmembrane proteins including:
| Agent | Mechanism | Status |
|---|---|---|
| Semaglintat | Gamma-secretase inhibitor | Halted in AD |
| Avagacestat | Gamma-secretase modulator | Halted in AD |
| MRK-560 | Selective gamma-secretase modulator | Preclinical |
De Strooper et al. Nicastrin function in gamma-secretase (2022). 2022. ↩︎
Zhang et al. Gamma-secretase and Alzheimer's disease (2021). 2021. ↩︎
Haapasalo & Kovacs, Gamma-secretase modulators (2021). 2021. ↩︎
Dorint et al. Nicastrin structure (2020). 2020. ↩︎