Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

PSEN1 encodes a protein called presenilin 1. It cuts other proteins into smaller pieces called peptides. It is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus and is essential for the normal maturation and division hair and skin cells. It is also involved in normal immune system function (R).

Mutations can cause Alzheimer's and skin and heart disorders (R)

Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) in the brain, which suggest presenilin-1 plays an important role in beta-amyloid regulation and can be highly related to Alzheimer's disease.^[22] 

     Alzheimer disease More than 150 PSEN1 gene mutations have been identified in patients with early-onset Alzheimer disease, a degenerative brain condition that begins before age 65. Mutations in the PSEN1 gene are the most common cause of early-onset Alzheimer disease, accounting for up to 70 percent of cases. Almost all PSEN1 gene mutations change single building blocks of DNA (nucleotides) in a particular segment of the PSEN1 gene. These mutations result in the production of an abnormal presenilin 1 protein. Defective presenilin 1 interferes with the function of the γ-secretase complex, which alters the processing of APP and leads to the overproduction of a longer, toxic version of amyloid-β peptide. Copies of this protein fragment stick together and build up in the brain, forming clumps called amyloid plaques that are a characteristic feature of Alzheimer disease. A buildup of toxic amyloid-β peptide and the formation of amyloid plaques likely lead to the death of neurons and the progressive signs and symptoms of this disorder. familial dilated cardiomyopathy Genetics Home Reference provides information about familial dilated cardiomyopathy. hidradenitis suppurativa At least one mutation in the PSEN1 gene has been found to cause hidradenitis suppurativa, a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin that develop in hair follicles. The nodules tend to become inflamed and painful, and they produce significant scarring as they heal. The identified mutation deletes a single DNA building block (nucleotide) from the PSEN1 gene, written as 725delC. This genetic change reduces the amount of functional presenilin 1 produced in cells, so less of this protein is available to act as part of the γ-secretase complex. The resulting shortage of normal γ-secretase impairs cell signaling pathways, including Notch signaling. Although little is known about the mechanism, studies suggest that abnormal Notch signaling may promote the development of recurrent nodules in hair follicles and trigger inflammation in the skin. Studies suggest that the PSEN1 gene mutation that causes hidradenitis suppurativa has a different effect on γ-secretase function than the mutations that cause early-onset Alzheimer disease. These differences may explain why no single PSEN1 gene mutation has been reported to cause the signs and symptoms of both diseases.

     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 maturation and division 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.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• PPAR-gamma1
• PPAR-gamma2
• p53
• C/EBPalpha
• p300

Tissue specificity:

Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes.

Molecular Function:

• Endopeptidase Activity
• Aspartic-Type Endopeptidase Activity
• Calcium Channel Activity
• Beta-Catenin Binding
• Pdz Domain Binding
• Cadherin Binding

Biological Processes:

• Autophagosome Assembly
• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Activation Of Mapkk Activity
• Blood Vessel Development
• Cell Fate Specification
• Somitogenesis
• Neuron Migration
• Positive Regulation Of Receptor Recycling
• Heart Looping
• Hematopoietic Progenitor Cell Differentiation
• T Cell Activation Involved In Immune Response
• Neural Retina Development
• Protein Glycosylation
• Membrane Protein Ectodomain Proteolysis
• Mitochondrial Transport
• Cellular Response To Dna Damage Stimulus
• Response To Oxidative Stress
• Negative Regulation Of Epidermal Growth Factor-Activated Receptor Activity
• Notch Signaling Pathway
• Notch Receptor Processing
• Memory
• Post-Embryonic Development
• Protein Transport
• L-Glutamate Transport
• Choline Transport
• Synaptic Vesicle Targeting
• Single Organismal Cell-Cell Adhesion
• Protein Processing
• Cerebral Cortex Cell Migration
• Cajal-Retzius Cell Differentiation
• Dorsal/Ventral Neural Tube Patterning
• Embryonic Limb Morphogenesis
• Positive Regulation Of Proteasomal Ubiquitin-Dependent Protein Catabolic Process
• Endoplasmic Reticulum Calcium Ion Homeostasis
• Beta-Amyloid Formation
• Intracellular Signal Transduction
• Regulation Of Phosphorylation
• Amyloid Precursor Protein Catabolic Process
• Myeloid Dendritic Cell Differentiation
• Positive Regulation Of Apoptotic Process
• Negative Regulation Of Apoptotic Process
• Positive Regulation Of Catalytic Activity
• Positive Regulation Of Map Kinase Activity
• Negative Regulation Of Neuron Apoptotic Process
• Skin Morphogenesis
• Positive Regulation Of Transcription, Dna-Templated
• Regulation Of Synaptic Plasticity
• Thymus Development
• Neuron Development
• Skeletal System Morphogenesis
• Brain Morphogenesis
• Epithelial Cell Proliferation
• Negative Regulation Of Axonogenesis
• Positive Regulation Of Coagulation
• T Cell Receptor Signaling Pathway
• Neuron Apoptotic Process
• Negative Regulation Of Ubiquitin-Protein Transferase Activity
• Smooth Endoplasmic Reticulum Calcium Ion Homeostasis
• Regulation Of Synaptic Transmission, Glutamatergic
• Canonical Wnt Signaling Pathway
• Regulation Of Resting Membrane Potential
• Positive Regulation Of Dendritic Spine Development
• Negative Regulation Of Protein Ubiquitination Involved In Ubiquitin-Dependent Protein Catabolic Process
• Negative Regulation Of Apoptotic Signaling Pathway

*synonyms