Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009, Article ID 327360, 14 pages
http://dx.doi.org/10.1155/2009/327360
Review Article

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

1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
2Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249-1664, USA
3Electron Microscopy Research Center, College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249-1664, USA
4Department of Cytology, Histology and Embryology, Azerbaijan Medical University, Baku AZ10-25, Azerbaijan
5Department of Psychiatry, Wroclaw Medical University, Wroclaw 50-229, Poland
6School of Health Science and Healthcare Administration, University of Atlanta, Atlanta, GA 30360, USA

Received 17 September 2009; Accepted 16 November 2009

Academic Editor: Janusz K. Rybakowski

Copyright © 2009 Mark E. Obrenovich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.