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

Neurobiol Aging. 2008 Mar;29(3):379-96. doi: 10.1016/j.neurobiolaging.2006.10.012. Epub 2006 Nov 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arrestins / metabolism*
  • Cohort Studies
  • Dementia / complications
  • Dementia / metabolism*
  • Female
  • G-Protein-Coupled Receptor Kinase 3 / metabolism*
  • G-Protein-Coupled Receptor Kinase 5 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / metabolism*
  • Postmortem Changes
  • Up-Regulation / physiology*


  • Arrestins
  • G-Protein-Coupled Receptor Kinase 3
  • G-Protein-Coupled Receptor Kinase 5