Dopamine depletion alters the balance between CA2+/calmodulin-dependent protein kinase II and protein phosphatase I

Abstract

MOLECULAR PHYSIOLOGY AND BIOPHYSICS

DOPAMINE DEPLETION ALTERS THE BALANCE BETWEEN CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE II AND PROTEIN PHOSPHATASE I

ABIGAIL M. BROWN Dissertation under the direction of Professor Roger J. Colbran

Parkinson’s disease is characterized by the preferential loss of the nigrostriatal dopaminergic neurons, whose axons terminate within the striatum and release dopamine onto medium spiny neurons. Striatal dopamine loss results in several changes in striatal medium spiny neuron morphology and disrupts corticostriatal synaptic plasticity. However, the molecular and biochemical mechanisms underlying the consequences of dopamine loss in Parkinson’s disease are not well understood. This dissertation presents evidence linking both short-term and chronic dopamine loss to the misregulation of two key synaptic signaling enzymes in the striatum, CaMKII and PP1. Although it is unclear what causes Parkinson’s disease in most human patients, the possibility that such striatal calcium-sensitive signaling pathways are misregulated suggests that targeting these pathways may be a useful strategy in developing future treatments for Parkinson’s disease.