Proteasome Activity in Parkinsonism through D1 Dopamine Receptor

As of today, L-DOPA is recognized as the most efficacious drug to alleviate the typical signs and symptoms of Parkinson disease (PD). It is most effective for the akinetic symtoms, and its use is indicated when the disease becomes disabling or it cannot be controlled by other antiparkinsonian drugs. Unfortunately, response to medication changes during the progression of the disease, with the patients developing tolerance to treatment and the need for higher doses that lead to the development of side effects. The Ubiquitine-proteosome system (UPS) is key in regulating the degradation of normal and abnormal intracellular proteins linked to signal transduction, cell cycle progression, apoptosis and differenciation; therefore it dysregulation would be expected to impact several systems. UPS dysregulation has been implicated in cancer, neurodegenerative and autoimmune diseases.