Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease
Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/9067 |
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| author | Daniela Baracaldo-Santamaría Sara Sofia Avendaño-Lopez Daniel Felipe Ariza-Salamanca Mateo Rodriguez-Giraldo Carlos A. Calderon-Ospina Rodrigo E. González-Reyes Mauricio O. Nava-Mesa |
| author_facet | Daniela Baracaldo-Santamaría Sara Sofia Avendaño-Lopez Daniel Felipe Ariza-Salamanca Mateo Rodriguez-Giraldo Carlos A. Calderon-Ospina Rodrigo E. González-Reyes Mauricio O. Nava-Mesa |
| author_sort | Daniela Baracaldo-Santamaría |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-β (Aβ), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation. |
| first_indexed | 2024-03-11T03:38:45Z |
| format | Article |
| id | doaj.art-9bde9e80d9b94ef6be7e799ab14fb8b9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:38:45Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9bde9e80d9b94ef6be7e799ab14fb8b92023-11-18T01:46:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410906710.3390/ijms24109067Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s DiseaseDaniela Baracaldo-Santamaría0Sara Sofia Avendaño-Lopez1Daniel Felipe Ariza-Salamanca2Mateo Rodriguez-Giraldo3Carlos A. Calderon-Ospina4Rodrigo E. González-Reyes5Mauricio O. Nava-Mesa6Pharmacology Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, ColombiaPharmacology Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, ColombiaMedical and Health Sciences Education Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, ColombiaGrupo de Investigación en Neurociencias (NeURos), Centro de Neurociencias Neurovitae-UR, Instituto de Medicina Traslacional (IMT), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá 111221, ColombiaPharmacology Unit, Department of Biomedical Sciences, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, ColombiaGrupo de Investigación en Neurociencias (NeURos), Centro de Neurociencias Neurovitae-UR, Instituto de Medicina Traslacional (IMT), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá 111221, ColombiaGrupo de Investigación en Neurociencias (NeURos), Centro de Neurociencias Neurovitae-UR, Instituto de Medicina Traslacional (IMT), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá 111221, ColombiaAlzheimer’s disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-β (Aβ), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.https://www.mdpi.com/1422-0067/24/10/9067Alzheimer’s diseasedementiacalcium channelscalciumtherapycalcium homeostasis |
| spellingShingle | Daniela Baracaldo-Santamaría Sara Sofia Avendaño-Lopez Daniel Felipe Ariza-Salamanca Mateo Rodriguez-Giraldo Carlos A. Calderon-Ospina Rodrigo E. González-Reyes Mauricio O. Nava-Mesa Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease dementia calcium channels calcium therapy calcium homeostasis |
| title | Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease |
| title_full | Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease |
| title_fullStr | Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease |
| title_full_unstemmed | Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease |
| title_short | Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease |
| title_sort | role of calcium modulation in the pathophysiology and treatment of alzheimer s disease |
| topic | Alzheimer’s disease dementia calcium channels calcium therapy calcium homeostasis |
| url | https://www.mdpi.com/1422-0067/24/10/9067 |
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