PSEN1 : presenilin 1

Description

The PSEN1 (presenilin 1) is a protein-coding gene located on chromosome 14.

The PSEN1 gene provides instructions for making a protein called presenilin 1. This protein is one part (subunit) of a complex called gamma- (γ-) secretase. Presenilin 1 carries out the major function of the complex, which is to cut apart (cleave) other proteins into smaller pieces called peptides. This process is called proteolysis, and presenilin 1 is described as the proteolytic subunit of γ-secretase.The γ-secretase complex is located in the membrane that surrounds cells, where it cleaves many different proteins that span the cell membrane (transmembrane proteins). This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways, known as Notch signaling, is essential for the normal growth and maturation (differentiation) of hair follicle cells and other types of skin cells.  Notch signaling is also involved in normal immune system function.The γ-secretase complex  may be best known for its role in processing amyloid precursor protein (APP), which is made in the brain and other tissues. γ-secretase cuts APP into smaller peptides, including soluble amyloid precursor protein (sAPP) and several versions of amyloid-beta (β) peptide. Evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells (neurons) in the brain both before and after birth. Other functions of sAPP and amyloid-β peptide are under investigation.

PSEN1 encodes presenilin-1, a key component of the gamma-secretase complex. This complex acts as an endoprotease, cleaving transmembrane proteins like Notch receptors and APP (amyloid-beta precursor protein). This cleavage is essential for various cellular processes, including Notch and Wnt signaling, cell-cell adhesion, and calcium homeostasis. PSEN1's role in APP processing is particularly noteworthy as it produces amyloid-beta peptides, which have been implicated in Alzheimer's disease. PSEN1's function relies on the presence of other gamma-secretase components, and it interacts with various proteins involved in diverse cellular pathways. Mutations in PSEN1 can lead to neurodevelopmental disorders and Alzheimer's disease, highlighting its critical role in human health.

PSEN1 is also known as ACNINV3, AD3, FAD, PS-1, PS1, PSNL1, S182.

Associated Diseases

• Cardiomyopathy, dilated, 1U
• Pick disease of brain
• Acne inversa, familial, 3
• Alzheimer disease 3
• Familial isolated dilated cardiomyopathy
• Progressive non-fluent aphasia
• Semantic dementia
• Early-onset autosomal dominant Alzheimer disease
• Behavioral variant of frontotemporal dementia
• Frontotemporal dementia
• Alzheimer disease
• Hidradenitis suppurativa
• Familial dilated cardiomyopathy