Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

Bychkov, E.R.; Gurevich, V.V.; Joyce, J.N.; Benovic, J.L.; Gurevich, E.V.

doi:10.1016/j.neurobiolaging.2006.10.012

« Previous Next »Neurobiology of Aging
Volume 29, Issue 3 , Pages 379-396, March 2008

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

E.R. Bychkov
- Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Laboratory of Neuroimmunology, Institute of Human Brain, St. Petersburg 197376, Russia
V.V. Gurevich
- Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
J.N. Joyce
- Parkinson's Disease Research Center, Sun Health Research Institute, Sun City, AZ 85351, USA
J.L. Benovic
- Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
E.V. Gurevich
- Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Corresponding author at: Department of Pharmacology, Vanderbilt University Medical Center, Preston Research Building Room 422, Nashville, TN 37232, United States. Tel.: +1 615 936 2720; fax: +1 615 343 6532.

Received 13 June 2006; received in revised form 4 September 2006; accepted 11 October 2006. published online 26 November 2006.

Abstract

Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors. We investigated changes in the expression of arrestins and GRKs in the striatum of patients with Parkinson's disease without (PD) or with dementia (PDD) at postmortem using Western blotting and ribonuclease protection assay. Both PD and PDD groups had similar degree of dopamine depletion in all striatal regions. Arrestin proteins and mRNAs were increased in the PDD group throughout striatum. Protein and mRNA of GRK5, the major subtype in the human striatum, and GRK3 were also upregulated, whereas GRK2 and 6 were mostly unchanged. The PD group had lower concentration of arrestins and GRKs than the PDD group. There was no statistical link between the load of Alzheimer's pathology and the expression of these signaling proteins. Upregulation of arrestins and GRK in PDD may confer resistance to the therapeutic effects of levodopa often observed in these patients. In addition, increased arrestin and GRK concentrations may lead to dementia via perturbation of multiple signaling mechanisms.

Keywords: Arrestin, G proteins-coupled receptor kinases, Parkinson's disease, Parkinson's disease with dementia, Signaling mechanisms