Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression
A multifactorial syndrome, Alzheimer’s disease is the main cause of dementia, but there is no existing therapy to prevent it or stop its progression. One of the earliest events of Alzheimer’s disease is the disruption of calcium homeostasis but that is just a prelude to the disease’s devastating imp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/8/393 |
| _version_ | 1797585121154433024 |
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| author | Danton H. O’Day |
| author_facet | Danton H. O’Day |
| author_sort | Danton H. O’Day |
| collection | DOAJ |
| description | A multifactorial syndrome, Alzheimer’s disease is the main cause of dementia, but there is no existing therapy to prevent it or stop its progression. One of the earliest events of Alzheimer’s disease is the disruption of calcium homeostasis but that is just a prelude to the disease’s devastating impact. Calcium does not work alone but must interact with downstream cellular components of which the small regulatory protein calmodulin is central, if not primary. This review supports the idea that, due to calcium dyshomeostasis, calmodulin is a dominant regulatory protein that functions in all stages of Alzheimer’s disease, and these regulatory events are impacted by amyloid beta. Amyloid beta not only binds to and regulates calmodulin but also multiple calmodulin-binding proteins involved in Alzheimer’s. Together, they act on the regulation of calcium dyshomeostasis, neuroinflammation, amyloidogenesis, memory formation, neuronal plasticity and more. The complex interactions between calmodulin, its binding proteins and amyloid beta may explain why many therapies have failed or are doomed to failure unless they are considered. |
| first_indexed | 2024-03-11T00:02:28Z |
| format | Article |
| id | doaj.art-86f79ce1eb6a415883446077d5e88add |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-11T00:02:28Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-86f79ce1eb6a415883446077d5e88add2023-11-19T00:41:33ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-07-014586246626110.3390/cimb45080393Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through ProgressionDanton H. O’Day0Department of Biology, University of Toronto Mississauga, Mississauga, ON L5L 1C6, CanadaA multifactorial syndrome, Alzheimer’s disease is the main cause of dementia, but there is no existing therapy to prevent it or stop its progression. One of the earliest events of Alzheimer’s disease is the disruption of calcium homeostasis but that is just a prelude to the disease’s devastating impact. Calcium does not work alone but must interact with downstream cellular components of which the small regulatory protein calmodulin is central, if not primary. This review supports the idea that, due to calcium dyshomeostasis, calmodulin is a dominant regulatory protein that functions in all stages of Alzheimer’s disease, and these regulatory events are impacted by amyloid beta. Amyloid beta not only binds to and regulates calmodulin but also multiple calmodulin-binding proteins involved in Alzheimer’s. Together, they act on the regulation of calcium dyshomeostasis, neuroinflammation, amyloidogenesis, memory formation, neuronal plasticity and more. The complex interactions between calmodulin, its binding proteins and amyloid beta may explain why many therapies have failed or are doomed to failure unless they are considered.https://www.mdpi.com/1467-3045/45/8/393Alzheimer’s diseasecalcium dysregulationcalmodulincalmodulin-binding proteinsamyloid betaion channels |
| spellingShingle | Danton H. O’Day Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression Current Issues in Molecular Biology Alzheimer’s disease calcium dysregulation calmodulin calmodulin-binding proteins amyloid beta ion channels |
| title | Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression |
| title_full | Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression |
| title_fullStr | Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression |
| title_full_unstemmed | Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression |
| title_short | Alzheimer’s Disease beyond Calcium Dysregulation: The Complex Interplay between Calmodulin, Calmodulin-Binding Proteins and Amyloid Beta from Disease Onset through Progression |
| title_sort | alzheimer s disease beyond calcium dysregulation the complex interplay between calmodulin calmodulin binding proteins and amyloid beta from disease onset through progression |
| topic | Alzheimer’s disease calcium dysregulation calmodulin calmodulin-binding proteins amyloid beta ion channels |
| url | https://www.mdpi.com/1467-3045/45/8/393 |
| work_keys_str_mv | AT dantonhoday alzheimersdiseasebeyondcalciumdysregulationthecomplexinterplaybetweencalmodulincalmodulinbindingproteinsandamyloidbetafromdiseaseonsetthroughprogression |