The GRK2 Overexpression Is a Primary Hallmark of Mitochondrial Lesions During Early Alzheimer Disease

Overview

Journal Cardiovasc Psychiatry Neurol

Specialty Cardiology & Vascular Diseases

Date 2010 Mar 6

PMID 20204079

Citations 28

Authors

Mark E Obrenovich

Hector H Palacios

Eldar Gasimov

Jerzy Leszek

Gjumrakch Aliev

Affiliations

Soon will be listed here.

Abstract

Increasing evidence points to vascular damage as an early contributor to the development of two leading causes of age-associated dementia, namely Alzheimer disease (AD) and AD-like pathology such as stroke. This review focuses on the role of G protein-coupled receptor kinases (GRKs) as they relate to dementia and how the cardio and cerebrovasculature is involved in AD pathogenesis. The exploration of GRKs in AD pathogenesis may help bridge gaps in our understanding of the heart-brain connection in relation to neurovisceral damage and vascular complications of AD. The a priori basis for this inquiry stems from the fact that kinases of this family regulate numerous receptor functions in the brain, myocardium and elsewhere. The aim of this review is to discuss the finding of GRK2 overexpression in the context of early AD pathogenesis. 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 through the cerebrovasculature. Finally, we synthesize this newer information in an attempt to put it into context with GRKs as regulators of cellular function, which makes these proteins potential diagnostic and therapeutic targets for future pharmacological intervention.

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