Alzheimer's disease: Is there a relationship between brain renin-angiotensin system, estradiol and glucose transporter-4 (GLUT-4)?

María Pilar Carrera-González; María Jesús Ramírez-Expósito; Carmen Guerrero-González; José Manuel Martínez-Martos; María Pilar Carrera-González; María Jesús Ramírez-Expósito; Carmen Guerrero-González; José Manuel Martínez-Martos

doi:10.3934/molsci.2023004

AIMS Molecular Science

2023, Volume 10, Issue 1: 37-51. doi: 10.3934/molsci.2023004

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Alzheimer's disease: Is there a relationship between brain renin-angiotensin system, estradiol and glucose transporter-4 (GLUT-4)?

1.
Experimental and Clinical Physiopathology Research Group, Department of Health Sciences, Faculty of Health Sciences, University of Jaén, E-23071 Jaén, Spain
2.
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba (UCO), Reina Sofia University Hospital (HURS), Cordoba, Spain

Received: 14 October 2022 Revised: 22 December 2022 Accepted: 27 January 2023 Published: 07 February 2023

One of the diseases more related to the continuous aging of the population is Alzheimer's disease, which is a type of dementia currently without either effective diagnosis biomarkers or treatments. Its higher prevalence in women makes it necessary to study pathways/systems that could participate and/or be involved in its development, as well as those that could be affected by hormonal factors, which, in this case, are estradiol levels. In this sense, one of the systems under study that is gaining special relevance in the scientific community is the brain renin-angiotensin system and its regulatory proteolytic enzymes. This system is strongly modulated by estrogens, and it is also connected with the cerebral glucose metabolism through the angiotensin IV receptor, also recognized as the insulin-regulated aminopeptidase (IRAP). Due to the fact that the cerebral glucose metabolism is highly compromised in patients with Alzheimer's disease, it is necessary to know the elements of the systems and their functions in this process, namely, the cerebral renin-angiotensin system, estradiol and IRAP, an enzyme and receptor co-localized in brain tissue with the insulin-dependent glucose transporter 4 (GLUT4). Knowledge of the connection between them could shed light on the molecular mechanisms of this disease and also provide new diagnostic and therapeutic targets.
- Alzheimer's disease,
- women,
- estrogen,
- insulin-regulated aminopeptidase,
- glucose transporter
Citation: María Pilar Carrera-González, María Jesús Ramírez-Expósito, Carmen Guerrero-González, José Manuel Martínez-Martos. Alzheimer's disease: Is there a relationship between brain renin-angiotensin system, estradiol and glucose transporter-4 (GLUT-4)?[J]. AIMS Molecular Science, 2023, 10(1): 37-51. doi: 10.3934/molsci.2023004

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Abstract

One of the diseases more related to the continuous aging of the population is Alzheimer's disease, which is a type of dementia currently without either effective diagnosis biomarkers or treatments. Its higher prevalence in women makes it necessary to study pathways/systems that could participate and/or be involved in its development, as well as those that could be affected by hormonal factors, which, in this case, are estradiol levels. In this sense, one of the systems under study that is gaining special relevance in the scientific community is the brain renin-angiotensin system and its regulatory proteolytic enzymes. This system is strongly modulated by estrogens, and it is also connected with the cerebral glucose metabolism through the angiotensin IV receptor, also recognized as the insulin-regulated aminopeptidase (IRAP). Due to the fact that the cerebral glucose metabolism is highly compromised in patients with Alzheimer's disease, it is necessary to know the elements of the systems and their functions in this process, namely, the cerebral renin-angiotensin system, estradiol and IRAP, an enzyme and receptor co-localized in brain tissue with the insulin-dependent glucose transporter 4 (GLUT4). Knowledge of the connection between them could shed light on the molecular mechanisms of this disease and also provide new diagnostic and therapeutic targets.

Conflict of interest

The authors declare no conflict of interest.

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