Gi/o-Protein Coupled Receptors in the Aging Brain
Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00089/full |
| _version_ | 1798043626510483456 |
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| author | Patrícia G. de Oliveira Marta L. S. Ramos António J. Amaro Roberto A. Dias Sandra I. Vieira |
| author_facet | Patrícia G. de Oliveira Marta L. S. Ramos António J. Amaro Roberto A. Dias Sandra I. Vieira |
| author_sort | Patrícia G. de Oliveira |
| collection | DOAJ |
| description | Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer’s and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages. |
| first_indexed | 2024-04-11T22:51:42Z |
| format | Article |
| id | doaj.art-5435e7b824e641949de36c69cc82e458 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-11T22:51:42Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-5435e7b824e641949de36c69cc82e4582022-12-22T03:58:34ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-04-011110.3389/fnagi.2019.00089442665Gi/o-Protein Coupled Receptors in the Aging BrainPatrícia G. de Oliveira0Marta L. S. Ramos1António J. Amaro2Roberto A. Dias3Sandra I. Vieira4Department of Medical Sciences, Institute of Biomedicine (iBiMED) and The Discovery CTR, Universidade de Aveiro, Aveiro, PortugalDepartment of Medical Sciences, Institute of Biomedicine (iBiMED) and The Discovery CTR, Universidade de Aveiro, Aveiro, PortugalSchool of Health Sciences (ESSUA), Universidade de Aveiro, Aveiro, PortugalDepartment of Medical Sciences, Institute of Biomedicine (iBiMED) and The Discovery CTR, Universidade de Aveiro, Aveiro, PortugalDepartment of Medical Sciences, Institute of Biomedicine (iBiMED) and The Discovery CTR, Universidade de Aveiro, Aveiro, PortugalCells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer’s and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.https://www.frontiersin.org/article/10.3389/fnagi.2019.00089/fullG protein-coupled receptors GPCRsGi/o heterotrimeric G proteinsagingreceptor density and binding potentialfrontal cortexhippocampus |
| spellingShingle | Patrícia G. de Oliveira Marta L. S. Ramos António J. Amaro Roberto A. Dias Sandra I. Vieira Gi/o-Protein Coupled Receptors in the Aging Brain Frontiers in Aging Neuroscience G protein-coupled receptors GPCRs Gi/o heterotrimeric G proteins aging receptor density and binding potential frontal cortex hippocampus |
| title | Gi/o-Protein Coupled Receptors in the Aging Brain |
| title_full | Gi/o-Protein Coupled Receptors in the Aging Brain |
| title_fullStr | Gi/o-Protein Coupled Receptors in the Aging Brain |
| title_full_unstemmed | Gi/o-Protein Coupled Receptors in the Aging Brain |
| title_short | Gi/o-Protein Coupled Receptors in the Aging Brain |
| title_sort | gi o protein coupled receptors in the aging brain |
| topic | G protein-coupled receptors GPCRs Gi/o heterotrimeric G proteins aging receptor density and binding potential frontal cortex hippocampus |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00089/full |
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