Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks
Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β (Aβ) formation. Besides its e...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/10/2166 |
| _version_ | 1797552625707646976 |
|---|---|
| author | Paola Pizzo Emy Basso Riccardo Filadi Elisa Greotti Alessandro Leparulo Diana Pendin Nelly Redolfi Michela Rossini Nicola Vajente Tullio Pozzan Cristina Fasolato |
| author_facet | Paola Pizzo Emy Basso Riccardo Filadi Elisa Greotti Alessandro Leparulo Diana Pendin Nelly Redolfi Michela Rossini Nicola Vajente Tullio Pozzan Cristina Fasolato |
| author_sort | Paola Pizzo |
| collection | DOAJ |
| description | Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β (Aβ) formation. Besides its enzymatic activity, PS2 is a multifunctional protein, being specifically involved, independently of γ-secretase activity, in the modulation of several cellular processes, such as Ca<sup>2+</sup> signalling, mitochondrial function, inter-organelle communication, and autophagy. As for the former, evidence has accumulated that supports the involvement of PS2 at different levels, ranging from organelle Ca<sup>2+</sup> handling to Ca<sup>2+</sup> entry through plasma membrane channels. Thus FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability. In this contribution, we summarize the main findings on PS2, primarily as a modulator of Ca<sup>2+</sup> homeostasis, with particular emphasis on the role of its mutations in the pathogenesis of FAD. Identification of cell pathways and molecules that are specifically targeted by PS2 mutants, as well as of common targets shared with PS1 mutants, will be fundamental to disentangle the complexity of memory loss and brain degeneration that occurs in Alzheimer’s disease (AD). |
| first_indexed | 2024-03-10T16:03:43Z |
| format | Article |
| id | doaj.art-77b7dcffd7784e8b81cd1a266393c925 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:03:43Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-77b7dcffd7784e8b81cd1a266393c9252023-11-20T15:03:01ZengMDPI AGCells2073-44092020-09-01910216610.3390/cells9102166Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain NetworksPaola Pizzo0Emy Basso1Riccardo Filadi2Elisa Greotti3Alessandro Leparulo4Diana Pendin5Nelly Redolfi6Michela Rossini7Nicola Vajente8Tullio Pozzan9Cristina Fasolato10Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyDepartment of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padua, ItalyPresenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β (Aβ) formation. Besides its enzymatic activity, PS2 is a multifunctional protein, being specifically involved, independently of γ-secretase activity, in the modulation of several cellular processes, such as Ca<sup>2+</sup> signalling, mitochondrial function, inter-organelle communication, and autophagy. As for the former, evidence has accumulated that supports the involvement of PS2 at different levels, ranging from organelle Ca<sup>2+</sup> handling to Ca<sup>2+</sup> entry through plasma membrane channels. Thus FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability. In this contribution, we summarize the main findings on PS2, primarily as a modulator of Ca<sup>2+</sup> homeostasis, with particular emphasis on the role of its mutations in the pathogenesis of FAD. Identification of cell pathways and molecules that are specifically targeted by PS2 mutants, as well as of common targets shared with PS1 mutants, will be fundamental to disentangle the complexity of memory loss and brain degeneration that occurs in Alzheimer’s disease (AD).https://www.mdpi.com/2073-4409/9/10/2166presenilin-2calcium signallingAlzheimer’s disease mouse modelsSOCEmitochondriaautophagy |
| spellingShingle | Paola Pizzo Emy Basso Riccardo Filadi Elisa Greotti Alessandro Leparulo Diana Pendin Nelly Redolfi Michela Rossini Nicola Vajente Tullio Pozzan Cristina Fasolato Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks Cells presenilin-2 calcium signalling Alzheimer’s disease mouse models SOCE mitochondria autophagy |
| title | Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks |
| title_full | Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks |
| title_fullStr | Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks |
| title_full_unstemmed | Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks |
| title_short | Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks |
| title_sort | presenilin 2 and calcium handling molecules organelles cells and brain networks |
| topic | presenilin-2 calcium signalling Alzheimer’s disease mouse models SOCE mitochondria autophagy |
| url | https://www.mdpi.com/2073-4409/9/10/2166 |
| work_keys_str_mv | AT paolapizzo presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT emybasso presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT riccardofiladi presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT elisagreotti presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT alessandroleparulo presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT dianapendin presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT nellyredolfi presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT michelarossini presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT nicolavajente presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT tulliopozzan presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks AT cristinafasolato presenilin2andcalciumhandlingmoleculesorganellescellsandbrainnetworks |