Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation.
Insights into cerebrovascular complications and Alzheimer disease through the selective loss of GRK2 regulation.
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DOI：
10.1111/j.1582-4934.2008.00512.x
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发表时间：
2009-05
影响因子：
5.3
通讯作者：
Aliev G
中科院分区：
文献类型：
--
作者：
Obrenovich ME;Morales LA;Cobb CJ;Shenk JC;Méndez GM;Fischbach K;Smith MA;Qasimov EK;Perry G;Aliev G
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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影响因子：
4.8
作者：
Carman, CV;Lisanti, MP;Benovic, JL
通讯作者：
Benovic, JL
DOI：
10.1016/s0006-8993(01)03046-3
发表时间：
2001-11-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Erdtmann-Vourliotis, M;Mayer, P;Höllt, V
通讯作者：
Höllt, V
影响因子：
4.8
作者：
Choi, DJ;Koch, WJ;Rockman, HA
通讯作者：
Rockman, HA
DOI：
10.1046/j.1432-1327.1998.2550363.x
发表时间：
1998-07-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Haga, K;Ogawa, H;Murofushi, H
通讯作者：
Murofushi, H
影响因子：
4.4
作者：
Aliev, G;Smith, MA;Perry, G
通讯作者：
Perry, G