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Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene

Presenilin-1 (PSEN1) has been verified as an important causative factor for early onset Alzheimer’s disease (EOAD). PSEN1 is a part of γ-secretase, and in addition to amyloid precursor protein (APP) cleavage, it can also affect other processes, such as Notch signaling, β-cadherin processing, and cal...

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Autores principales: Bagaria, Jaya, Bagyinszky, Eva, An, Seong Soo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504248/
https://www.ncbi.nlm.nih.gov/pubmed/36142879
http://dx.doi.org/10.3390/ijms231810970
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author Bagaria, Jaya
Bagyinszky, Eva
An, Seong Soo A.
author_facet Bagaria, Jaya
Bagyinszky, Eva
An, Seong Soo A.
author_sort Bagaria, Jaya
collection PubMed
description Presenilin-1 (PSEN1) has been verified as an important causative factor for early onset Alzheimer’s disease (EOAD). PSEN1 is a part of γ-secretase, and in addition to amyloid precursor protein (APP) cleavage, it can also affect other processes, such as Notch signaling, β-cadherin processing, and calcium metabolism. Several motifs and residues have been identified in PSEN1, which may play a significant role in γ-secretase mechanisms, such as the WNF, GxGD, and PALP motifs. More than 300 mutations have been described in PSEN1; however, the clinical phenotypes related to these mutations may be diverse. In addition to classical EOAD, patients with PSEN1 mutations regularly present with atypical phenotypic symptoms, such as spasticity, seizures, and visual impairment. In vivo and in vitro studies were performed to verify the effect of PSEN1 mutations on EOAD. The pathogenic nature of PSEN1 mutations can be categorized according to the ACMG-AMP guidelines; however, some mutations could not be categorized because they were detected only in a single case, and their presence could not be confirmed in family members. Genetic modifiers, therefore, may play a critical role in the age of disease onset and clinical phenotypes of PSEN1 mutations. This review introduces the role of PSEN1 in γ-secretase, the clinical phenotypes related to its mutations, and possible significant residues of the protein.
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spelling pubmed-95042482022-09-24 Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene Bagaria, Jaya Bagyinszky, Eva An, Seong Soo A. Int J Mol Sci Review Presenilin-1 (PSEN1) has been verified as an important causative factor for early onset Alzheimer’s disease (EOAD). PSEN1 is a part of γ-secretase, and in addition to amyloid precursor protein (APP) cleavage, it can also affect other processes, such as Notch signaling, β-cadherin processing, and calcium metabolism. Several motifs and residues have been identified in PSEN1, which may play a significant role in γ-secretase mechanisms, such as the WNF, GxGD, and PALP motifs. More than 300 mutations have been described in PSEN1; however, the clinical phenotypes related to these mutations may be diverse. In addition to classical EOAD, patients with PSEN1 mutations regularly present with atypical phenotypic symptoms, such as spasticity, seizures, and visual impairment. In vivo and in vitro studies were performed to verify the effect of PSEN1 mutations on EOAD. The pathogenic nature of PSEN1 mutations can be categorized according to the ACMG-AMP guidelines; however, some mutations could not be categorized because they were detected only in a single case, and their presence could not be confirmed in family members. Genetic modifiers, therefore, may play a critical role in the age of disease onset and clinical phenotypes of PSEN1 mutations. This review introduces the role of PSEN1 in γ-secretase, the clinical phenotypes related to its mutations, and possible significant residues of the protein. MDPI 2022-09-19 /pmc/articles/PMC9504248/ /pubmed/36142879 http://dx.doi.org/10.3390/ijms231810970 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bagaria, Jaya
Bagyinszky, Eva
An, Seong Soo A.
Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title_full Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title_fullStr Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title_full_unstemmed Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title_short Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
title_sort genetics, functions, and clinical impact of presenilin-1 (psen1) gene
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504248/
https://www.ncbi.nlm.nih.gov/pubmed/36142879
http://dx.doi.org/10.3390/ijms231810970
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