Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease
The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=31;epage=37;aulast=Hernandez-Sapiens |
| _version_ | 1818435774626922496 |
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| author | Mercedes A Hernandez-Sapiens Edwin E Reza-Zaldívar Ana L Márquez-Aguirre Ulises Gómez-Pinedo Jorge Matias-Guiu Ricardo R Cevallos Juan C Mateos-Díaz Víctor J Sánchez-González Alejandro A Canales-Aguirre |
| author_facet | Mercedes A Hernandez-Sapiens Edwin E Reza-Zaldívar Ana L Márquez-Aguirre Ulises Gómez-Pinedo Jorge Matias-Guiu Ricardo R Cevallos Juan C Mateos-Díaz Víctor J Sánchez-González Alejandro A Canales-Aguirre |
| author_sort | Mercedes A Hernandez-Sapiens |
| collection | DOAJ |
| description | The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease. Furthermore, we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment. |
| first_indexed | 2024-12-14T16:58:14Z |
| format | Article |
| id | doaj.art-66a250d50ba443c4bb6eeff003fa364d |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-14T16:58:14Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-66a250d50ba443c4bb6eeff003fa364d2022-12-21T22:53:54ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742022-01-01171313710.4103/1673-5374.313016Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s diseaseMercedes A Hernandez-SapiensEdwin E Reza-ZaldívarAna L Márquez-AguirreUlises Gómez-PinedoJorge Matias-GuiuRicardo R CevallosJuan C Mateos-DíazVíctor J Sánchez-GonzálezAlejandro A Canales-AguirreThe presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease. Furthermore, we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=31;epage=37;aulast=Hernandez-Sapiensfamilial alzheimer’s disease; familial alzheimer’s disease-induced pluripotent stem cells models; induced pluripotent stem cells; neurogenesis; neuronal differentiation; notch; presenilin 1; psen1 mutations; γ-secretase complex |
| spellingShingle | Mercedes A Hernandez-Sapiens Edwin E Reza-Zaldívar Ana L Márquez-Aguirre Ulises Gómez-Pinedo Jorge Matias-Guiu Ricardo R Cevallos Juan C Mateos-Díaz Víctor J Sánchez-González Alejandro A Canales-Aguirre Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease Neural Regeneration Research familial alzheimer’s disease; familial alzheimer’s disease-induced pluripotent stem cells models; induced pluripotent stem cells; neurogenesis; neuronal differentiation; notch; presenilin 1; psen1 mutations; γ-secretase complex |
| title | Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease |
| title_full | Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease |
| title_fullStr | Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease |
| title_full_unstemmed | Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease |
| title_short | Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease |
| title_sort | presenilin mutations and their impact on neuronal differentiation in alzheimer s disease |
| topic | familial alzheimer’s disease; familial alzheimer’s disease-induced pluripotent stem cells models; induced pluripotent stem cells; neurogenesis; neuronal differentiation; notch; presenilin 1; psen1 mutations; γ-secretase complex |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=31;epage=37;aulast=Hernandez-Sapiens |
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