# Presenilin-1

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Presenilin-1
> Markdown URL: https://mediated.wiki/source/Presenilin-1.md
> Source: https://en.wikipedia.org/wiki/Presenilin-1
> Source revision: 1323246360
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

Protein-coding gene in the species Homo sapiens

PSEN1 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KR6, 5A63, 4UIS, 5FN3, 5FN4, 5FN5, 5FN2 Identifiers Aliases PSEN1, Psen1, Ad3h, PS-1, PS1, S182, AD3, FAD, presenilin 1, ACNINV3 External IDs OMIM: 104311; MGI: 1202717; HomoloGene: 7186; GeneCards: PSEN1; OMA:PSEN1 - orthologs Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q24.2 Start 73,136,418 bp[1] End 73,223,691 bp[1] Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 D1|12 38.84 cM Start 83,734,926 bp[2] End 83,781,973 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle frontal gyrus corpus callosum C1 segment monocyte rectum Achilles tendon mucosa of ileum sural nerve amniotic fluid blood Top expressed in transitional epithelium of urinary bladder seminiferous tubule primary oocyte left colon submandibular gland granulocyte ileum ankle spermatid zygote More reference expression data BioGPS More reference expression data Gene ontology Molecular function PDZ domain binding cadherin binding peptidase activity beta-catenin binding protein binding calcium channel activity aspartic-type endopeptidase activity endopeptidase activity hydrolase activity aspartic endopeptidase activity, intramembrane cleaving Cellular component nuclear membrane membrane mitochondrion ciliary rootlet neuron projection gamma-secretase complex nucleus kinetochore centrosome rough endoplasmic reticulum dendritic shaft aggresome cell surface membrane-bounded organelle endoplasmic reticulum membrane raft Golgi apparatus growth cone neuromuscular junction intracellular anatomical structure axon nuclear outer membrane endoplasmic reticulum membrane Golgi membrane integral component of plasma membrane smooth endoplasmic reticulum lysosomal membrane cell junction dendrite presynapse mitochondrial inner membrane cytoplasmic vesicle cytoplasm plasma membrane cell cortex integral component of membrane azurophil granule membrane Z discdkac soma perinuclear region of cytoplasm early endosome synaptic vesicle protein-containing complex sarcolemma synapse synaptic membrane integral component of presynaptic membrane endosome early endosome membrane cell projection Biological process negative regulation of neuron apoptotic process somitogenesis positive regulation of protein phosphorylation positive regulation of MAP kinase activity positive regulation of catalytic activity mitochondrial transport post-embryonic development positive regulation of dendritic spine development cellular response to DNA damage stimulus heart looping blood vessel development membrane protein ectodomain proteolysis regulation of epidermal growth factor-activated receptor activity regulation of resting membrane potential regulation of synaptic transmission, glutamatergic amyloid precursor protein catabolic process apoptotic process thymus development positive regulation of coagulation negative regulation of apoptotic signaling pathway neuron development memory endoplasmic reticulum calcium ion homeostasis response to oxidative stress autophagosome assembly positive regulation of transcription, DNA-templated development of the heart negative regulation of axonogenesis embryonic limb morphogenesis locomotion learning or memory protein transport cerebral cortex cell migration positive regulation of proteasomal ubiquitin-dependent protein catabolic process L-glutamate transmembrane transport brain morphogenesis Notch signaling pathway negative regulation of protein phosphorylation myeloid leukocyte differentiation neuron apoptotic process smooth endoplasmic reticulum calcium ion homeostasis synaptic vesicle targeting Cajal-Retzius cell differentiation skin morphogenesis negative regulation of protein kinase activity cell fate specification skeletal system morphogenesis regulation of phosphorylation cellular calcium ion homeostasis epithelial cell proliferation neuron migration negative regulation of apoptotic process negative regulation of transcription by RNA polymerase II proteolysis regulation of synaptic plasticity negative regulation of epidermal growth factor-activated receptor activity cell adhesion hematopoietic progenitor cell differentiation neuron differentiation cerebral cortex development canonical Wnt signaling pathway dorsal/ventral neural tube patterning neural retina development positive regulation of protein kinase activity T cell activation involved in immune response neurogenesis intracellular signal transduction protein processing protein maturation myeloid dendritic cell differentiation autophagy protein glycosylation brain development negative regulation of ubiquitin-protein transferase activity choline transport positive regulation of apoptotic process Notch receptor processing negative regulation of ubiquitin-dependent protein catabolic process forebrain development regulation of protein binding T cell receptor signaling pathway segmentation positive regulation of receptor recycling calcium ion transmembrane transport amyloid-beta formation amyloid precursor protein metabolic process neutrophil degranulation regulation of canonical Wnt signaling pathway amyloid-beta metabolic process positive regulation of L-glutamate import across plasma membrane astrocyte activation involved in immune response regulation of neuron projection development cerebellum development positive regulation of protein binding Notch receptor processing, ligand-dependent positive regulation of phosphorylation astrocyte activation synapse organization cell-cell adhesion cellular response to amyloid-beta negative regulation of core promoter binding negative regulation of low-density lipoprotein receptor activity positive regulation of amyloid fibril formation neuron projection maintenance membrane protein intracellular domain proteolysis positive regulation of protein import into nucleus ephrin receptor signaling pathway positive regulation of gene expression negative regulation of gene expression positive regulation of glycolytic process Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 5663 19164 Ensembl ENSG00000080815 ENSMUSG00000019969 UniProt P49768 P49769 RefSeq (mRNA) NM_000021 NM_007318 NM_007319 NM_008943 NM_001362271 RefSeq (protein) NP_000012 NP_015557 NP_001349200 Location (UCSC) Chr 14: 73.14 – 73.22 Mb Chr 12: 83.73 – 83.78 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Presenilin-1** **(PS-1)** is a [presenilin](/source/Presenilin) [protein](/source/Protein) that in humans is encoded by the *PSEN1* [gene](/source/Gene).[5] Presenilin-1 is one of the four core proteins in the [gamma secretase](/source/Gamma_secretase) complex, which is considered to play an important role in generation of [amyloid beta](/source/Amyloid_beta) (Aβ) from [amyloid-beta precursor protein](/source/Amyloid-beta_precursor_protein) (APP). Accumulation of amyloid beta is associated with the onset of [Alzheimer's disease](/source/Alzheimer's_disease).[6]

## Structure

Presenilin possesses a 9 transmembrane domain topology, with an [extracellular](/source/Extracellular) [C-terminus](/source/C-terminus) and a [cytosolic](/source/Cytosolic) [N-terminus](/source/N-terminus).[7][8] Presenilin undergoes endo-[proteolytic](/source/Proteolytic) processing to produce ~27-28 [kDa](/source/KDa) N-terminal and ~16-17 kDa C-terminal fragments in humans.[9] Furthermore, presenilin exists in the cell mainly as a [heterodimer](/source/Heterodimer) of the C-terminal and N-terminus fragments.[9] When presenilin 1 is overexpressed, the full length protein accumulates in an inactive form.[10] Based on evidence that a gamma-secretase inhibitor binds to the fragments,[11] the cleaved presenilin complex is considered to be the active form.[12]

## Function

Presenilins are postulated to regulate APP processing through their effects on [gamma secretase](/source/Gamma_secretase), an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the [Notch receptor](/source/Notch_signaling), such that they either directly regulate [gamma secretase](/source/Gamma_secretase) activity or themselves are [protease](/source/Protease) enzymes. Multiple alternatively spliced transcript variants have been identified for this gene, the full-length natures of only some have been determined.[13]

### Notch signaling pathway

In Notch signaling, critical proteolytic reactions takes place during maturation and activation of Notch membrane receptor.[14] Notch1 is cleaved extracellularlly at site1 (S1) and two polypeptides are produced to form a heterodimer receptor on the cell surface.[15] After the formation of receptor, Notch1 is further cleaved in site 3(S3)[16] and release Notch1 intracellular domain (NICD) from the membrane.[17]

Presenilin 1 has been shown to play an important role in proteolytic process. In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype.[18] Moreover, in mammalian cells, deficiency of PSEN1 also causes the defect in the proteolytic release of NICD from a truncated Notch construct. The same step can be also blocked by several gamma-secretase inhibitors, shown in the same study.[19] These evidences collectively suggest a critical role of presenilin 1 in the Notch signaling pathway.

### Wnt signaling pathway

[Wnt signaling pathway](/source/Wnt_signaling_pathway) has been shown to be involved in several critical steps in embryogenesis and development. Presenilin 1 has been shown to form a complex with [beta-catenin](/source/Beta-catenin), an important component in Wnt signaling, and stabilize beta-catenin.[20] Mutant of presenilin-1 that reduces the ability to stabilize beta-catenin complex leads to hyperactive degradation of beta-catenin in the brains of transgenic mice.[20]

Considered as a negative regulator in Wnt signaling pathway, presenilin-1 was also found to play a role in beta-catenin phosphorylation.[21] Beta-catenin is coupled by presenilin-1 and undergoes a sequential phosphorylation by two kinase activities.[21] The study also further illustrates that the deficiency of presenilin 1 disconnects the sequential phosphorylation and thus disrupts the normal wnt signaling pathway.[21]

## Clinical significance

### Beta-amyloid production

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] Further study conducted in neuronal cultures derived from presenilin-1 deficient mouse embryos showed that cleavage by alpha- and beta- secretase was still normal without the presence of presenilin-1. Meanwhile, when the cleavage by gamma-cleavage of the transmembrane domain of APP was abolished a 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can downregulate amyloid and inhibition of presenilin-1 can be a potential method for anti-amyloidogenic therapy in Alzheimer's disease.[23] Extensive study on the role of presenilin-1 in amyloid production has been conducted to improve our understanding of Alzheimer's disease.[24][25]

### Alzheimer's disease

[Alzheimer's disease](/source/Alzheimer's_disease) (AD) patients with an inherited form of the disease may carry mutations in the presenilin proteins (PSEN1; [PSEN2](/source/PSEN2)) or the [amyloid precursor protein](/source/Amyloid_precursor_protein) (APP). These disease-linked mutations result in increased production of the longer form of [amyloid beta](/source/Amyloid_beta) (main component of [amyloid](/source/Amyloid) deposits found in AD brains). These mutations result in early-onset Alzheimer's Disease, which is a rare form of the disease. These rare genetic variants are autosomal dominant.[26]

### Cancer

In addition to its role in Alzheimer's disease, presenilin-1 also found to be important in cancer. A study of broad range gene expression was conducted on human [melanoma](/source/Melanoma). Researchers classified the melanoma cell lines into two types. The study showed that presenilin-1 is down regulated in this cell type while it is overexpressed in the other cell type.[27] Another study on multidrug resistance (MDR) cell line also reveals a role of presenilin-1 in cancer development. Because of the development to the resistance to chemicals, MDR cells become a critical factor on the success of cancer chemotherapy.[28] In the study, researchers tried to explore the molecular mechanism by looking into the expression of Notch1 intracellular (N1IC) domain and presenilin 1. They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 ([ABCC1](/source/ABCC1)) was also found to be regulated by N1IC, which suggest a mechanism of ABCC1 regulated by presenilin 1 and notch signaling.[29]

## Interactions

PSEN1 has been shown to [interact](/source/Protein-protein_interaction) with:

- [BCL2](/source/Bcl-2),[30]

- [CTNNB1](/source/Beta-catenin),[31][32][33]

- [CTNND1](/source/CTNND1),[34]

- [FLNB](/source/FLNB),[35]

- [GFAP](/source/Glial_fibrillary_acidic_protein),[36]

- [Delta catenin](/source/Delta_catenin),[37]

- [ICAM5](/source/ICAM5),[38]

- [KCNIP3](/source/Calsenilin),[39][40]

- [NCSTN](/source/Nicastrin),[41][42][43][44][45]

- [PKP4](/source/PKP4),[46] and

- [UBQLN1](/source/UBQLN1).[47]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000080815](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000080815) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000019969](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000019969) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=5663). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=19164). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid1411576_5-0)** Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, White JA, Bonnycastle L, Weber JL, Alonso ME (Nov 1992). "Genetic linkage evidence for a familial Alzheimer's seasesease locus on chromosome 14". *Science*. **258** (5082): 668–71. [Bibcode](/source/Bibcode_(identifier)):[1992Sci...258..668S](https://ui.adsabs.harvard.edu/abs/1992Sci...258..668S). [doi](/source/Doi_(identifier)):[10.1126/science.1411576](https://doi.org/10.1126%2Fscience.1411576). [PMID](/source/PMID_(identifier)) [1411576](https://pubmed.ncbi.nlm.nih.gov/1411576).

1. **[^](#cite_ref-pmid7888181_6-0)** Selkoe DJ (1994). "Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease". *Annu. Rev. Cell Biol*. **10**: 373–403. [doi](/source/Doi_(identifier)):[10.1146/annurev.cb.10.110194.002105](https://doi.org/10.1146%2Fannurev.cb.10.110194.002105). [PMID](/source/PMID_(identifier)) [7888181](https://pubmed.ncbi.nlm.nih.gov/7888181).

1. **[^](#cite_ref-pmid16046406_7-0)** Laudon H, Hansson EM, Melén K, Bergman A, Farmery MR, Winblad B, Lendahl U, [von Heijne G](/source/Gunnar_von_Heijne), Näslund J (October 2005). ["A nine-transmembrane domain topology for presenilin 1"](https://doi.org/10.1074%2Fjbc.M507217200). *J. Biol. Chem*. **280** (42): 35352–60. [doi](/source/Doi_(identifier)):[10.1074/jbc.M507217200](https://doi.org/10.1074%2Fjbc.M507217200). [PMID](/source/PMID_(identifier)) [16046406](https://pubmed.ncbi.nlm.nih.gov/16046406).

1. **[^](#cite_ref-pmid18256384_8-0)** Spasic D, Annaert W (February 2008). "Building gamma-secretase: the bits and pieces". *J. Cell Sci*. **121** (Pt 4): 413–20. [doi](/source/Doi_(identifier)):[10.1242/jcs.015255](https://doi.org/10.1242%2Fjcs.015255). [PMID](/source/PMID_(identifier)) [18256384](https://pubmed.ncbi.nlm.nih.gov/18256384).

1. ^ [***a***](#cite_ref-Thinakaran_1996_9-0) [***b***](#cite_ref-Thinakaran_1996_9-1) Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, Kim G, Ratovitsky T, Davenport F, Nordstedt C, Seeger M, Hardy J, Levey AI, Gandy SE, Jenkins NA, Copeland NG, Price DL, Sisodia SS (July 1996). ["Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo"](https://doi.org/10.1016%2FS0896-6273%2800%2980291-3). *Neuron*. **17** (1): 181–90. [doi](/source/Doi_(identifier)):[10.1016/S0896-6273(00)80291-3](https://doi.org/10.1016%2FS0896-6273%2800%2980291-3). [PMID](/source/PMID_(identifier)) [8755489](https://pubmed.ncbi.nlm.nih.gov/8755489).

1. **[^](#cite_ref-pmid9305918_10-0)** Ratovitski T, Slunt HH, Thinakaran G, Price DL, Sisodia SS, Borchelt DR (September 1997). ["Endoproteolytic processing and stabilization of wild-type and mutant presenilin"](https://doi.org/10.1074%2Fjbc.272.39.24536). *J. Biol. Chem*. **272** (39): 24536–41. [doi](/source/Doi_(identifier)):[10.1074/jbc.272.39.24536](https://doi.org/10.1074%2Fjbc.272.39.24536). [PMID](/source/PMID_(identifier)) [9305918](https://pubmed.ncbi.nlm.nih.gov/9305918).

1. **[^](#cite_ref-pmid10864326_11-0)** Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ (June 2000). "Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1". *Nature*. **405** (6787): 689–94. [Bibcode](/source/Bibcode_(identifier)):[2000Natur.405..689L](https://ui.adsabs.harvard.edu/abs/2000Natur.405..689L). [doi](/source/Doi_(identifier)):[10.1038/35015085](https://doi.org/10.1038%2F35015085). [PMID](/source/PMID_(identifier)) [10864326](https://pubmed.ncbi.nlm.nih.gov/10864326). [S2CID](/source/S2CID_(identifier)) [4420032](https://api.semanticscholar.org/CorpusID:4420032).

1. **[^](#cite_ref-pmid15866047_12-0)** Brunkan AL, Martinez M, Walker ES, Goate AM (May 2005). "Presenilin endoproteolysis is an intramolecular cleavage". *Mol. Cell. Neurosci*. **29** (1): 65–73. [doi](/source/Doi_(identifier)):[10.1016/j.mcn.2004.12.012](https://doi.org/10.1016%2Fj.mcn.2004.12.012). [PMID](/source/PMID_(identifier)) [15866047](https://pubmed.ncbi.nlm.nih.gov/15866047). [S2CID](/source/S2CID_(identifier)) [37048469](https://api.semanticscholar.org/CorpusID:37048469).

1. **[^](#cite_ref-13)** ["Entrez Gene: PSEN1 presenilin 1 (Alzheimer disease 3)"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5663).

1. **[^](#cite_ref-pmid9727485_14-0)** Chan YM, Jan YN (August 1998). ["Roles for proteolysis and trafficking in notch maturation and signal transduction"](https://doi.org/10.1016%2FS0092-8674%2800%2981583-4). *Cell*. **94** (4): 423–6. [doi](/source/Doi_(identifier)):[10.1016/S0092-8674(00)81583-4](https://doi.org/10.1016%2FS0092-8674%2800%2981583-4). [PMID](/source/PMID_(identifier)) [9727485](https://pubmed.ncbi.nlm.nih.gov/9727485).

1. **[^](#cite_ref-pmid9653148_15-0)** Logeat F, Bessia C, Brou C, LeBail O, Jarriault S, Seidah NG, Israël A (July 1998). ["The Notch1 receptor is cleaved constitutively by a furin-like convertase"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20937). *Proc. Natl. Acad. Sci. U.S.A*. **95** (14): 8108–12. [Bibcode](/source/Bibcode_(identifier)):[1998PNAS...95.8108L](https://ui.adsabs.harvard.edu/abs/1998PNAS...95.8108L). [doi](/source/Doi_(identifier)):[10.1073/pnas.95.14.8108](https://doi.org/10.1073%2Fpnas.95.14.8108). [PMC](/source/PMC_(identifier)) [20937](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20937). [PMID](/source/PMID_(identifier)) [9653148](https://pubmed.ncbi.nlm.nih.gov/9653148).

1. **[^](#cite_ref-pmid9620803_16-0)** Schroeter EH, Kisslinger JA, Kopan R (May 1998). "Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain". *Nature*. **393** (6683): 382–6. [Bibcode](/source/Bibcode_(identifier)):[1998Natur.393..382S](https://ui.adsabs.harvard.edu/abs/1998Natur.393..382S). [doi](/source/Doi_(identifier)):[10.1038/30756](https://doi.org/10.1038%2F30756). [PMID](/source/PMID_(identifier)) [9620803](https://pubmed.ncbi.nlm.nih.gov/9620803). [S2CID](/source/S2CID_(identifier)) [4431882](https://api.semanticscholar.org/CorpusID:4431882).

1. **[^](#cite_ref-pmid7566092_17-0)** Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A (September 1995). "Signalling downstream of activated mammalian Notch". *Nature*. **377** (6547): 355–8. [Bibcode](/source/Bibcode_(identifier)):[1995Natur.377..355J](https://ui.adsabs.harvard.edu/abs/1995Natur.377..355J). [doi](/source/Doi_(identifier)):[10.1038/377355a0](https://doi.org/10.1038%2F377355a0). [PMID](/source/PMID_(identifier)) [7566092](https://pubmed.ncbi.nlm.nih.gov/7566092). [S2CID](/source/S2CID_(identifier)) [4269110](https://api.semanticscholar.org/CorpusID:4269110).

1. **[^](#cite_ref-pmid10206646_18-0)** Struhl G, Greenwald I (April 1999). "Presenilin is required for activity and nuclear access of Notch in Drosophila". *Nature*. **398** (6727): 522–5. [Bibcode](/source/Bibcode_(identifier)):[1999Natur.398..522S](https://ui.adsabs.harvard.edu/abs/1999Natur.398..522S). [doi](/source/Doi_(identifier)):[10.1038/19091](https://doi.org/10.1038%2F19091). [PMID](/source/PMID_(identifier)) [10206646](https://pubmed.ncbi.nlm.nih.gov/10206646). [S2CID](/source/S2CID_(identifier)) [4392625](https://api.semanticscholar.org/CorpusID:4392625).

1. **[^](#cite_ref-pmid10206645_19-0)** De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (April 1999). "A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain". *Nature*. **398** (6727): 518–22. [Bibcode](/source/Bibcode_(identifier)):[1999Natur.398..518D](https://ui.adsabs.harvard.edu/abs/1999Natur.398..518D). [doi](/source/Doi_(identifier)):[10.1038/19083](https://doi.org/10.1038%2F19083). [PMID](/source/PMID_(identifier)) [10206645](https://pubmed.ncbi.nlm.nih.gov/10206645). [S2CID](/source/S2CID_(identifier)) [4346474](https://api.semanticscholar.org/CorpusID:4346474).

1. ^ [***a***](#cite_ref-Zhang_2009_20-0) [***b***](#cite_ref-Zhang_2009_20-1) Zhang C, Wu B, Beglopoulos V, Wines-Samuelson M, Zhang D, Dragatsis I, Südhof TC, Shen J (July 2009). ["Presenilins are essential for regulating neurotransmitter release"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744588). *Nature*. **460** (7255): 632–6. [Bibcode](/source/Bibcode_(identifier)):[2009Natur.460..632Z](https://ui.adsabs.harvard.edu/abs/2009Natur.460..632Z). [doi](/source/Doi_(identifier)):[10.1038/nature08177](https://doi.org/10.1038%2Fnature08177). [PMC](/source/PMC_(identifier)) [2744588](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744588). [PMID](/source/PMID_(identifier)) [19641596](https://pubmed.ncbi.nlm.nih.gov/19641596).

1. ^ [***a***](#cite_ref-Kang_2002_21-0) [***b***](#cite_ref-Kang_2002_21-1) [***c***](#cite_ref-Kang_2002_21-2) Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH (September 2002). ["Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis"](https://doi.org/10.1016%2FS0092-8674%2802%2900970-4). *Cell*. **110** (6): 751–62. [doi](/source/Doi_(identifier)):[10.1016/S0092-8674(02)00970-4](https://doi.org/10.1016%2FS0092-8674%2802%2900970-4). [PMID](/source/PMID_(identifier)) [12297048](https://pubmed.ncbi.nlm.nih.gov/12297048).

1. **[^](#cite_ref-pmid8878479_22-0)** Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S (October 1996). "Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1". *Nature*. **383** (6602): 710–3. [Bibcode](/source/Bibcode_(identifier)):[1996Natur.383..710D](https://ui.adsabs.harvard.edu/abs/1996Natur.383..710D). [doi](/source/Doi_(identifier)):[10.1038/383710a0](https://doi.org/10.1038%2F383710a0). [PMID](/source/PMID_(identifier)) [8878479](https://pubmed.ncbi.nlm.nih.gov/8878479). [S2CID](/source/S2CID_(identifier)) [4339658](https://api.semanticscholar.org/CorpusID:4339658).

1. **[^](#cite_ref-pmid9450754_23-0)** De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (January 1998). "Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein". *Nature*. **391** (6665): 387–90. [Bibcode](/source/Bibcode_(identifier)):[1998Natur.391..387D](https://ui.adsabs.harvard.edu/abs/1998Natur.391..387D). [doi](/source/Doi_(identifier)):[10.1038/34910](https://doi.org/10.1038%2F34910). [PMID](/source/PMID_(identifier)) [9450754](https://pubmed.ncbi.nlm.nih.gov/9450754). [S2CID](/source/S2CID_(identifier)) [4397720](https://api.semanticscholar.org/CorpusID:4397720).

1. **[^](#cite_ref-pmid15087467_24-0)** Pitsi D, Octave JN (June 2004). ["Presenilin 1 stabilizes the C-terminal fragment of the amyloid precursor protein independently of gamma-secretase activity"](https://doi.org/10.1074%2Fjbc.M312710200). *J. Biol. Chem*. **279** (24): 25333–8. [doi](/source/Doi_(identifier)):[10.1074/jbc.M312710200](https://doi.org/10.1074%2Fjbc.M312710200). [PMID](/source/PMID_(identifier)) [15087467](https://pubmed.ncbi.nlm.nih.gov/15087467).

1. **[^](#cite_ref-pmid12761548_25-0)** Phiel CJ, Wilson CA, Lee VM, Klein PS (May 2003). "GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides". *Nature*. **423** (6938): 435–9. [Bibcode](/source/Bibcode_(identifier)):[2003Natur.423..435P](https://ui.adsabs.harvard.edu/abs/2003Natur.423..435P). [doi](/source/Doi_(identifier)):[10.1038/nature01640](https://doi.org/10.1038%2Fnature01640). [PMID](/source/PMID_(identifier)) [12761548](https://pubmed.ncbi.nlm.nih.gov/12761548). [S2CID](/source/S2CID_(identifier)) [4416851](https://api.semanticscholar.org/CorpusID:4416851).

1. **[^](#cite_ref-pmid22908189_26-0)** Mayeux R, [Stern Y](/source/Yaakov_Stern) (2012). ["Epidemiology of Alzheimer disease"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821). *Cold Spring Harbor Perspectives in Medicine*. **2** (8) a006239. [doi](/source/Doi_(identifier)):[10.1101/cshperspect.a006239](https://doi.org/10.1101%2Fcshperspect.a006239). [PMC](/source/PMC_(identifier)) [3405821](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821). [PMID](/source/PMID_(identifier)) [22908189](https://pubmed.ncbi.nlm.nih.gov/22908189).

1. **[^](#cite_ref-pmid19383853_27-0)** Su DM, Zhang Q, Wang X, He P, Zhu YJ, Zhao J, Rennert OM, Su YA (May 2009). ["Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128982). *Mol. Cancer Ther*. **8** (5): 1292–304. [doi](/source/Doi_(identifier)):[10.1158/1535-7163.MCT-08-1030](https://doi.org/10.1158%2F1535-7163.MCT-08-1030). [PMC](/source/PMC_(identifier)) [3128982](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128982). [PMID](/source/PMID_(identifier)) [19383853](https://pubmed.ncbi.nlm.nih.gov/19383853).

1. **[^](#cite_ref-pmid11902585_28-0)** Gottesman MM, Fojo T, Bates SE (January 2002). ["Multidrug resistance in cancer: role of ATP-dependent transporters"](https://zenodo.org/record/1233500). *Nat. Rev. Cancer*. **2** (1): 48–58. [doi](/source/Doi_(identifier)):[10.1038/nrc706](https://doi.org/10.1038%2Fnrc706). [PMID](/source/PMID_(identifier)) [11902585](https://pubmed.ncbi.nlm.nih.gov/11902585). [S2CID](/source/S2CID_(identifier)) [34650170](https://api.semanticscholar.org/CorpusID:34650170).

1. **[^](#cite_ref-pmid22143792_29-0)** Cho S, Lu M, He X, Ee PL, Bhat U, Schneider E, Miele L, Beck WT (December 2011). ["Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251103). *Proc. Natl. Acad. Sci. U.S.A*. **108** (51): 20778–83. [Bibcode](/source/Bibcode_(identifier)):[2011PNAS..10820778C](https://ui.adsabs.harvard.edu/abs/2011PNAS..10820778C). [doi](/source/Doi_(identifier)):[10.1073/pnas.1019452108](https://doi.org/10.1073%2Fpnas.1019452108). [PMC](/source/PMC_(identifier)) [3251103](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251103). [PMID](/source/PMID_(identifier)) [22143792](https://pubmed.ncbi.nlm.nih.gov/22143792).

1. **[^](#cite_ref-pmid10521466_30-0)** Alberici A, Moratto D, Benussi L, Gasparini L, Ghidoni R, Gatta LB, Finazzi D, Frisoni GB, Trabucchi M, Growdon JH, Nitsch RM, Binetti G (October 1999). ["Presenilin 1 protein directly interacts with Bcl-2"](https://doi.org/10.1074%2Fjbc.274.43.30764). *J. Biol. Chem*. **274** (43): 30764–9. [doi](/source/Doi_(identifier)):[10.1074/jbc.274.43.30764](https://doi.org/10.1074%2Fjbc.274.43.30764). [PMID](/source/PMID_(identifier)) [10521466](https://pubmed.ncbi.nlm.nih.gov/10521466).

1. **[^](#cite_ref-pmid9852041_31-0)** Tesco G, Kim TW, Diehlmann A, Beyreuther K, Tanzi RE (December 1998). ["Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation"](https://doi.org/10.1074%2Fjbc.273.51.33909). *J. Biol. Chem*. **273** (51): 33909–14. [doi](/source/Doi_(identifier)):[10.1074/jbc.273.51.33909](https://doi.org/10.1074%2Fjbc.273.51.33909). [PMID](/source/PMID_(identifier)) [9852041](https://pubmed.ncbi.nlm.nih.gov/9852041).

1. **[^](#cite_ref-pmid10341227_32-0)** Kang DE, Soriano S, Frosch MP, Collins T, Naruse S, Sisodia SS, Leibowitz G, Levine F, Koo EH (June 1999). ["Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the beta-catenin-signaling pathway"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782616). *J. Neurosci*. **19** (11): 4229–37. [doi](/source/Doi_(identifier)):[10.1523/JNEUROSCI.19-11-04229.1999](https://doi.org/10.1523%2FJNEUROSCI.19-11-04229.1999). [PMC](/source/PMC_(identifier)) [6782616](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782616). [PMID](/source/PMID_(identifier)) [10341227](https://pubmed.ncbi.nlm.nih.gov/10341227).

1. **[^](#cite_ref-pmid9738936_33-0)** Murayama M, Tanaka S, Palacino J, Murayama O, Honda T, Sun X, Yasutake K, Nihonmatsu N, [Wolozin B](/source/Benjamin_Wolozin), Takashima A (August 1998). "Direct association of presenilin-1 with beta-catenin". *FEBS Lett*. **433** (1–2): 73–7. [doi](/source/Doi_(identifier)):[10.1016/S0014-5793(98)00886-2](https://doi.org/10.1016%2FS0014-5793%2898%2900886-2). [PMID](/source/PMID_(identifier)) [9738936](https://pubmed.ncbi.nlm.nih.gov/9738936). [S2CID](/source/S2CID_(identifier)) [85416623](https://api.semanticscholar.org/CorpusID:85416623).

1. **[^](#cite_ref-pmid10208590_34-0)** Tanahashi H, Tabira T (February 1999). "Isolation of human delta-catenin and its binding specificity with presenilin 1". *NeuroReport*. **10** (3): 563–8. [doi](/source/Doi_(identifier)):[10.1097/00001756-199902250-00022](https://doi.org/10.1097%2F00001756-199902250-00022). [PMID](/source/PMID_(identifier)) [10208590](https://pubmed.ncbi.nlm.nih.gov/10208590).

1. **[^](#cite_ref-pmid9437013_35-0)** Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February 1998). ["Interaction of presenilins with the filamin family of actin-binding proteins"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042137). *J. Neurosci*. **18** (3): 914–22. [doi](/source/Doi_(identifier)):[10.1523/JNEUROSCI.18-03-00914.1998](https://doi.org/10.1523%2FJNEUROSCI.18-03-00914.1998). [PMC](/source/PMC_(identifier)) [2042137](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042137). [PMID](/source/PMID_(identifier)) [9437013](https://pubmed.ncbi.nlm.nih.gov/9437013).

1. **[^](#cite_ref-pmid12058025_36-0)** Nielsen AL, Holm IE, Johansen M, Bonven B, Jørgensen P, Jørgensen AL (August 2002). ["A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins"](https://doi.org/10.1074%2Fjbc.M112121200). *J. Biol. Chem*. **277** (33): 29983–91. [doi](/source/Doi_(identifier)):[10.1074/jbc.M112121200](https://doi.org/10.1074%2Fjbc.M112121200). [PMID](/source/PMID_(identifier)) [12058025](https://pubmed.ncbi.nlm.nih.gov/12058025).

1. **[^](#cite_ref-37)** Levesque G (1999). "Presenilins interact with armadillo proteins including neural-specific plakophilin-related protein and beta-catenin". *Journal of Neurochemistry*. **72** (3): 999–1008. [doi](/source/Doi_(identifier)):[10.1046/j.1471-4159.1999.0720999.x](https://doi.org/10.1046%2Fj.1471-4159.1999.0720999.x). [PMID](/source/PMID_(identifier)) [10037471](https://pubmed.ncbi.nlm.nih.gov/10037471). [S2CID](/source/S2CID_(identifier)) [36124450](https://api.semanticscholar.org/CorpusID:36124450).

1. **[^](#cite_ref-pmid11719200_38-0)** Annaert WG, Esselens C, Baert V, Boeve C, Snellings G, Cupers P, Craessaerts K, De Strooper B (November 2001). ["Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins"](https://doi.org/10.1016%2FS0896-6273%2801%2900512-8). *Neuron*. **32** (4): 579–89. [doi](/source/Doi_(identifier)):[10.1016/S0896-6273(01)00512-8](https://doi.org/10.1016%2FS0896-6273%2801%2900512-8). [PMID](/source/PMID_(identifier)) [11719200](https://pubmed.ncbi.nlm.nih.gov/11719200).

1. **[^](#cite_ref-pmid9771752_39-0)** Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". *Nat. Med*. **4** (10): 1177–81. [doi](/source/Doi_(identifier)):[10.1038/2673](https://doi.org/10.1038%2F2673). [PMID](/source/PMID_(identifier)) [9771752](https://pubmed.ncbi.nlm.nih.gov/9771752). [S2CID](/source/S2CID_(identifier)) [10799492](https://api.semanticscholar.org/CorpusID:10799492).

1. **[^](#cite_ref-pmid10854253_40-0)** Kashiwa A, Yoshida H, Lee S, Paladino T, Liu Y, Chen Q, Dargusch R, Schubert D, Kimura H (July 2000). "Isolation and characterization of novel presenilin binding protein". *J. Neurochem*. **75** (1): 109–16. [doi](/source/Doi_(identifier)):[10.1046/j.1471-4159.2000.0750109.x](https://doi.org/10.1046%2Fj.1471-4159.2000.0750109.x). [PMID](/source/PMID_(identifier)) [10854253](https://pubmed.ncbi.nlm.nih.gov/10854253).

1. **[^](#cite_ref-pmid15257293_41-0)** Haffner C, Frauli M, Topp S, Irmler M, Hofmann K, Regula JT, Bally-Cuif L, Haass C (August 2004). ["Nicalin and its binding partner Nomo are novel Nodal signaling antagonists"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514924). *EMBO J*. **23** (15): 3041–50. [doi](/source/Doi_(identifier)):[10.1038/sj.emboj.7600307](https://doi.org/10.1038%2Fsj.emboj.7600307). [PMC](/source/PMC_(identifier)) [514924](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514924). [PMID](/source/PMID_(identifier)) [15257293](https://pubmed.ncbi.nlm.nih.gov/15257293).

1. **[^](#cite_ref-pmid14572442_42-0)** Baulac S, LaVoie MJ, Kimberly WT, Strahle J, Wolfe MS, Selkoe DJ, Xia W (November 2003). "Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates". *Neurobiol. Dis*. **14** (2): 194–204. [CiteSeerX](/source/CiteSeerX_(identifier)) [10.1.1.624.6715](https://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.624.6715). [doi](/source/Doi_(identifier)):[10.1016/S0969-9961(03)00123-2](https://doi.org/10.1016%2FS0969-9961%2803%2900123-2). [PMID](/source/PMID_(identifier)) [14572442](https://pubmed.ncbi.nlm.nih.gov/14572442). [S2CID](/source/S2CID_(identifier)) [53205510](https://api.semanticscholar.org/CorpusID:53205510).

1. **[^](#cite_ref-pmid12471034_43-0)** Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, Luthra A, Mount HT, Tandon A, Fraser PE, St George-Hyslop P (February 2003). ["APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes"](https://doi.org/10.1074%2Fjbc.M209499200). *J. Biol. Chem*. **278** (9): 7374–80. [doi](/source/Doi_(identifier)):[10.1074/jbc.M209499200](https://doi.org/10.1074%2Fjbc.M209499200). [PMID](/source/PMID_(identifier)) [12471034](https://pubmed.ncbi.nlm.nih.gov/12471034).

1. **[^](#cite_ref-pmid12297508_44-0)** Lee SF, Shah S, Li H, Yu C, Han W, Yu G (November 2002). ["Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch"](https://doi.org/10.1074%2Fjbc.M208164200). *J. Biol. Chem*. **277** (47): 45013–9. [doi](/source/Doi_(identifier)):[10.1074/jbc.M208164200](https://doi.org/10.1074%2Fjbc.M208164200). [PMID](/source/PMID_(identifier)) [12297508](https://pubmed.ncbi.nlm.nih.gov/12297508).

1. **[^](#cite_ref-pmid10993067_45-0)** Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (September 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". *Nature*. **407** (6800): 48–54. [Bibcode](/source/Bibcode_(identifier)):[2000Natur.407...48Y](https://ui.adsabs.harvard.edu/abs/2000Natur.407...48Y). [doi](/source/Doi_(identifier)):[10.1038/35024009](https://doi.org/10.1038%2F35024009). [PMID](/source/PMID_(identifier)) [10993067](https://pubmed.ncbi.nlm.nih.gov/10993067). [S2CID](/source/S2CID_(identifier)) [4339220](https://api.semanticscholar.org/CorpusID:4339220).

1. **[^](#cite_ref-pmid10092585_46-0)** Stahl B, Diehlmann A, Südhof TC (April 1999). ["Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071"](https://doi.org/10.1074%2Fjbc.274.14.9141). *J. Biol. Chem*. **274** (14): 9141–8. [doi](/source/Doi_(identifier)):[10.1074/jbc.274.14.9141](https://doi.org/10.1074%2Fjbc.274.14.9141). [PMID](/source/PMID_(identifier)) [10092585](https://pubmed.ncbi.nlm.nih.gov/10092585).

1. **[^](#cite_ref-pmid11076969_47-0)** Mah AL, Perry G, Smith MA, Monteiro MJ (November 2000). ["Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169435). *J. Cell Biol*. **151** (4): 847–62. [doi](/source/Doi_(identifier)):[10.1083/jcb.151.4.847](https://doi.org/10.1083%2Fjcb.151.4.847). [PMC](/source/PMC_(identifier)) [2169435](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169435). [PMID](/source/PMID_(identifier)) [11076969](https://pubmed.ncbi.nlm.nih.gov/11076969).

## Further reading

- Cruts M, Hendriks L, Van Broeckhoven C (1997). "The presenilin genes: a new gene family involved in Alzheimer disease pathology". *Hum. Mol. Genet*. 5 Spec No: 1449–55. [doi](/source/Doi_(identifier)):[10.1093/hmg/5.Supplement_1.1449](https://doi.org/10.1093%2Fhmg%2F5.Supplement_1.1449). [PMID](/source/PMID_(identifier)) [8875251](https://pubmed.ncbi.nlm.nih.gov/8875251).

- Cruts M, Van Broeckhoven C (1998). ["Presenilin mutations in Alzheimer's disease"](https://doi.org/10.1002%2F%28SICI%291098-1004%281998%2911%3A3%3C183%3A%3AAID-HUMU1%3E3.0.CO%3B2-J). *Hum. Mutat*. **11** (3): 183–90. [doi](/source/Doi_(identifier)):[10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J](https://doi.org/10.1002%2F%28SICI%291098-1004%281998%2911%3A3%3C183%3A%3AAID-HUMU1%3E3.0.CO%3B2-J). [PMID](/source/PMID_(identifier)) [9521418](https://pubmed.ncbi.nlm.nih.gov/9521418). [S2CID](/source/S2CID_(identifier)) [37870910](https://api.semanticscholar.org/CorpusID:37870910).

- Larner AJ, Doran M (2006). "Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene". *J. Neurol*. **253** (2): 139–58. [doi](/source/Doi_(identifier)):[10.1007/s00415-005-0019-5](https://doi.org/10.1007%2Fs00415-005-0019-5). [PMID](/source/PMID_(identifier)) [16267640](https://pubmed.ncbi.nlm.nih.gov/16267640). [S2CID](/source/S2CID_(identifier)) [19642313](https://api.semanticscholar.org/CorpusID:19642313).

- Wolfe MS (2007). ["When loss is gain: reduced presenilin proteolytic function leads to increased Aβ42/Aβ40. Talking Point on the role of presenilin mutations in Alzheimer disease"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796780). *EMBO Rep*. **8** (2): 136–40. [doi](/source/Doi_(identifier)):[10.1038/sj.embor.7400896](https://doi.org/10.1038%2Fsj.embor.7400896). [PMC](/source/PMC_(identifier)) [1796780](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796780). [PMID](/source/PMID_(identifier)) [17268504](https://pubmed.ncbi.nlm.nih.gov/17268504).

- De Strooper B (2007). ["Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796779). *EMBO Rep*. **8** (2): 141–6. [doi](/source/Doi_(identifier)):[10.1038/sj.embor.7400897](https://doi.org/10.1038%2Fsj.embor.7400897). [PMC](/source/PMC_(identifier)) [1796779](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796779). [PMID](/source/PMID_(identifier)) [17268505](https://pubmed.ncbi.nlm.nih.gov/17268505).

## External links

- [GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease](https://www.ncbi.nlm.nih.gov/books/NBK1236/)

v t e Protein: cell membrane proteins (other than Cell surface receptor, enzymes, and cytoskeleton) Arrestin SAG ARRB1 ARRB2 ARR3 Membrane-spanning 4A MS4A1 MS4A2 MS4A3 MS4A4A MS4A4E MS4A5 MS4A6A MS4A6E MS4A7 MS4A8B MS4A9 MS4A10 MS4A12 MS4A13 MS4A14 MS4A15 MS4A18 Myelin Myelin basic protein PMP2 Myelin proteolipid protein PLP1 Myelin oligodendrocyte glycoprotein Myelin-associated glycoprotein Myelin protein zero Pulmonary surfactant Pulmonary surfactant-associated protein B Pulmonary surfactant-associated protein C Tetraspanin TSPAN1 TSPAN2 TSPAN3 TSPAN4 TSPAN5 TSPAN6 TSPAN7 TSPAN8 TSPAN9 TSPAN10 TSPAN11 TSPAN12 TSPAN13 TSPAN14 TSPAN15 TSPAN16 TSPAN17 TSPAN18 TSPAN19 TSPAN20 TSPAN21 TSPAN22 TSPAN23 TSPAN24 TSPAN25 TSPAN26 TSPAN27 TSPAN28 TSPAN29 TSPAN30 TSPAN31 TSPAN32 TSPAN33 TSPAN34 Other/ungrouped Calnexin LDL-receptor-related protein-associated protein Neurofibromin 2 Presenilin PSEN1 PSEN2 HFE Phospholipid transfer proteins Dysferlin STRC OTOF see also other cell membrane protein disorders

---
Adapted from the Wikipedia article [Presenilin-1](https://en.wikipedia.org/wiki/Presenilin-1) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Presenilin-1?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.