The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases
The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dep...
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| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Aging Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5081021 |
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| author | Maulilio John Kipanyula Wahabu Hamisi Kimaro Paul F. Seke Etet |
| author_facet | Maulilio John Kipanyula Wahabu Hamisi Kimaro Paul F. Seke Etet |
| author_sort | Maulilio John Kipanyula |
| collection | DOAJ |
| description | The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects. |
| format | Article |
| id | doaj-art-6b8a740359e44b3495dab6426a0d4f9d |
| institution | Kabale University |
| issn | 2090-2204 2090-2212 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | Journal of Aging Research |
| spelling | doaj-art-6b8a740359e44b3495dab6426a0d4f9d2025-02-03T05:53:58ZengWileyJournal of Aging Research2090-22042090-22122016-01-01201610.1155/2016/50810215081021The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and DiseasesMaulilio John Kipanyula0Wahabu Hamisi Kimaro1Paul F. Seke Etet2Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Sokoine University of Agriculture, P.O. Box 3016, Chuo Kikuu, Morogoro, TanzaniaDepartment of Veterinary Anatomy, Faculty of Veterinary Medicine, Sokoine University of Agriculture, P.O. Box 3016, Chuo Kikuu, Morogoro, TanzaniaDepartment of Basic Health Sciences, Qassim University, Buraydah, Al-Qassim 51452, Saudi ArabiaThe ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.http://dx.doi.org/10.1155/2016/5081021 |
| spellingShingle | Maulilio John Kipanyula Wahabu Hamisi Kimaro Paul F. Seke Etet The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases Journal of Aging Research |
| title | The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases |
| title_full | The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases |
| title_fullStr | The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases |
| title_full_unstemmed | The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases |
| title_short | The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases |
| title_sort | emerging roles of the calcineurin nuclear factor of activated t lymphocytes pathway in nervous system functions and diseases |
| url | http://dx.doi.org/10.1155/2016/5081021 |
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