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Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation

Alzheimer disease (AD) and stroke are two leading causes of age-associated dementia. Increasing evidence points to vascular damage as an early contributor to the development of AD and AD-like pathology. In this review, we discuss the role of G protein-coupled receptor kinase 2 (GRK2) as it relates t...

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Autores principales: Obrenovich, Mark E, Morales, Ludis A, Cobb, Celia J, Shenk, Justin C, Méndez, Gina M, Fischbach, Kathryn, Smith, Mark A, Qasimov, Eldar K, Perry, George, Aliev, Gjumrakch
Formato: Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919803/
https://www.ncbi.nlm.nih.gov/pubmed/19292735
http://dx.doi.org/10.1111/j.1582-4934.2008.00512.x
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author Obrenovich, Mark E
Morales, Ludis A
Cobb, Celia J
Shenk, Justin C
Méndez, Gina M
Fischbach, Kathryn
Smith, Mark A
Qasimov, Eldar K
Perry, George
Aliev, Gjumrakch
author_facet Obrenovich, Mark E
Morales, Ludis A
Cobb, Celia J
Shenk, Justin C
Méndez, Gina M
Fischbach, Kathryn
Smith, Mark A
Qasimov, Eldar K
Perry, George
Aliev, Gjumrakch
author_sort Obrenovich, Mark E
collection PubMed
description Alzheimer disease (AD) and stroke are two leading causes of age-associated dementia. Increasing evidence points to vascular damage as an early contributor to the development of AD and AD-like pathology. In this review, we discuss the role of G protein-coupled receptor kinase 2 (GRK2) as it relates to individuals affected by AD and how the cardiovasculature plays a role in AD pathogenesis. The possible involvement of GRKs in AD pathogenesis is an interesting notion, which may help bridge the gap in our understanding of the heart–brain connection in relation to neurovisceral damage and vascular complications in AD, since kinases of this family are known to regulate numerous receptor functions both in the brain, myocardium, and elsewhere. The aim of this review is to discuss our findings of overexpression of GRK2 in the context of the early pathogenesis of AD, because increased levels of GRK2 immunoreactivity were found in vulnerable neurons of AD patients as well as in a two-vessel occlusion (2-VO) mammalian model of ischaemia. Also, we consider the consequences for this overexpression as a loss of G-protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis, particularly in the context of cerebrovascular disease. We synthesize this newer information and attempt to put it into context with GRKs as regulators of diverse physiological cellular functions that could be appropriate targets for future pharmacological intervention.
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spelling pubmed-29198032010-08-11 Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation Obrenovich, Mark E Morales, Ludis A Cobb, Celia J Shenk, Justin C Méndez, Gina M Fischbach, Kathryn Smith, Mark A Qasimov, Eldar K Perry, George Aliev, Gjumrakch J Cell Mol Med Reviews Alzheimer disease (AD) and stroke are two leading causes of age-associated dementia. Increasing evidence points to vascular damage as an early contributor to the development of AD and AD-like pathology. In this review, we discuss the role of G protein-coupled receptor kinase 2 (GRK2) as it relates to individuals affected by AD and how the cardiovasculature plays a role in AD pathogenesis. The possible involvement of GRKs in AD pathogenesis is an interesting notion, which may help bridge the gap in our understanding of the heart–brain connection in relation to neurovisceral damage and vascular complications in AD, since kinases of this family are known to regulate numerous receptor functions both in the brain, myocardium, and elsewhere. The aim of this review is to discuss our findings of overexpression of GRK2 in the context of the early pathogenesis of AD, because increased levels of GRK2 immunoreactivity were found in vulnerable neurons of AD patients as well as in a two-vessel occlusion (2-VO) mammalian model of ischaemia. Also, we consider the consequences for this overexpression as a loss of G-protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis, particularly in the context of cerebrovascular disease. We synthesize this newer information and attempt to put it into context with GRKs as regulators of diverse physiological cellular functions that could be appropriate targets for future pharmacological intervention. Blackwell Publishing Ltd 2009-05 2008-10-06 /pmc/articles/PMC2919803/ /pubmed/19292735 http://dx.doi.org/10.1111/j.1582-4934.2008.00512.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
spellingShingle Reviews
Obrenovich, Mark E
Morales, Ludis A
Cobb, Celia J
Shenk, Justin C
Méndez, Gina M
Fischbach, Kathryn
Smith, Mark A
Qasimov, Eldar K
Perry, George
Aliev, Gjumrakch
Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title_full Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title_fullStr Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title_full_unstemmed Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title_short Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation
title_sort insights into cerebrovascular complications and alzheimer disease through the selective loss of grk2 regulation
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919803/
https://www.ncbi.nlm.nih.gov/pubmed/19292735
http://dx.doi.org/10.1111/j.1582-4934.2008.00512.x
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