Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes. Calcineurin (CaN), a calcium/calmodulin-dependent serine/threonine phosphatase, is hyperactivated in AD, leading to enhanced neuroinflammation, synaptic...
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Elsevier
2025-06-01
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| Series: | Brain Disorders |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666459325000381 |
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| author | Awgichew Behaile Teklemariam Edgeit Abebe Zewde Melaku Mekonnen Agidew Sisay Ayalkibet Siyamrew Lemlemu Maru Zelalem Tilahun Muche |
| author_facet | Awgichew Behaile Teklemariam Edgeit Abebe Zewde Melaku Mekonnen Agidew Sisay Ayalkibet Siyamrew Lemlemu Maru Zelalem Tilahun Muche |
| author_sort | Awgichew Behaile Teklemariam |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes. Calcineurin (CaN), a calcium/calmodulin-dependent serine/threonine phosphatase, is hyperactivated in AD, leading to enhanced neuroinflammation, synaptic dysfunction, and tau hyperphosphorylation. Similarly, the dysregulation of ionotropic glutamate receptors (iGluRs), particularly NMDA receptors in the context of AD, aggravates excitotoxicity, which in turn contributes to neuronal damage and cognitive deficits. Moreover, AMPA and kainate receptors also play significant roles in synaptic plasticity and neurodegeneration.The intricate interplay between CaN and iGluRs, specifically NMDA, AMPA, and kainate receptors, through various signaling pathways plays a crucial role in AD pathogenesis. Therapeutic approaches targeting the CaN-iGluR axis, including CaN inhibitors and iGluR modulators, have the potential to mitigate the progression of AD and improve cognitive functions associated with the disease.This systematic review aims to consolidate current knowledge on the molecular mechanisms underlying CaN and iGluR dysregulation in AD and discuss their potential as therapeutic targets. Future investigations should prioritize elucidating the precise interactions between CaN and iGluRs, as well as developing selective modulators to enhance the efficacy and safety of therapeutic interventions for AD. |
| format | Article |
| id | doaj-art-80c2e3c5094d4308a9b784ffe07d0f9a |
| institution | Kabale University |
| issn | 2666-4593 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Disorders |
| spelling | doaj-art-80c2e3c5094d4308a9b784ffe07d0f9a2025-08-20T03:24:36ZengElsevierBrain Disorders2666-45932025-06-011810021810.1016/j.dscb.2025.100218Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic reviewAwgichew Behaile Teklemariam0Edgeit Abebe Zewde1Melaku Mekonnen Agidew2Sisay Ayalkibet Siyamrew3Lemlemu Maru4Zelalem Tilahun Muche5Department of Medical Biochemistry, College of Health Sciences, Debre Tabor University, P. O. Box: 272; Postal code: 6300, Debre Tabor, Ethiopia; Corresponding author.Department of Medical Physiology, College of Health Sciences, Debre Tabor University, Debre Tabor, EthiopiaDepartment of Medical Biochemistry, College of Health Sciences, Debre Tabor University, P. O. Box: 272; Postal code: 6300, Debre Tabor, EthiopiaDepartment of Pharmacy, Hossana Health Science College, Hossana, EthiopiaDepartment of Medical Physiology, School of Medicine, College of Health Sciences, University of Gondar, Gondar, EthiopiaDepartment of Medical Physiology, College of Health Sciences, Debre Tabor University, Debre Tabor, EthiopiaAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes. Calcineurin (CaN), a calcium/calmodulin-dependent serine/threonine phosphatase, is hyperactivated in AD, leading to enhanced neuroinflammation, synaptic dysfunction, and tau hyperphosphorylation. Similarly, the dysregulation of ionotropic glutamate receptors (iGluRs), particularly NMDA receptors in the context of AD, aggravates excitotoxicity, which in turn contributes to neuronal damage and cognitive deficits. Moreover, AMPA and kainate receptors also play significant roles in synaptic plasticity and neurodegeneration.The intricate interplay between CaN and iGluRs, specifically NMDA, AMPA, and kainate receptors, through various signaling pathways plays a crucial role in AD pathogenesis. Therapeutic approaches targeting the CaN-iGluR axis, including CaN inhibitors and iGluR modulators, have the potential to mitigate the progression of AD and improve cognitive functions associated with the disease.This systematic review aims to consolidate current knowledge on the molecular mechanisms underlying CaN and iGluR dysregulation in AD and discuss their potential as therapeutic targets. Future investigations should prioritize elucidating the precise interactions between CaN and iGluRs, as well as developing selective modulators to enhance the efficacy and safety of therapeutic interventions for AD.http://www.sciencedirect.com/science/article/pii/S2666459325000381Alzheimer's diseaseAMPACalcineuriniGluRsKainate receptorsNMDA |
| spellingShingle | Awgichew Behaile Teklemariam Edgeit Abebe Zewde Melaku Mekonnen Agidew Sisay Ayalkibet Siyamrew Lemlemu Maru Zelalem Tilahun Muche Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review Brain Disorders Alzheimer's disease AMPA Calcineurin iGluRs Kainate receptors NMDA |
| title | Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review |
| title_full | Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review |
| title_fullStr | Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review |
| title_full_unstemmed | Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review |
| title_short | Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review |
| title_sort | role of calcineurin and ionotropic glutamate receptors in alzheimer s disease a systematic review |
| topic | Alzheimer's disease AMPA Calcineurin iGluRs Kainate receptors NMDA |
| url | http://www.sciencedirect.com/science/article/pii/S2666459325000381 |
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