INTRODUCTION: In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Parkinson's disease. METHODS: Protein levels were assayed by western blotting in samples of caudate nucleus and putamen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergic function were also assayed. RESULTS: Levels of the transcription factor DeltaFosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from patients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both DeltaFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metabolites, and the dopamine transporter. CONCLUSIONS: These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of DeltaFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in DeltaFosB and RGS9 occur in humans with Parkinson's disease. Knowledge of these adaptations can help us understand the changes in striatal function associated with Parkinson's disease and assist in the development of novel treatments.
INTRODUCTION: In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Parkinson's disease. METHODS: Protein levels were assayed by western blotting in samples of caudate nucleus and putamen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergic function were also assayed. RESULTS: Levels of the transcription factor DeltaFosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from patients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both DeltaFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metabolites, and the dopamine transporter. CONCLUSIONS: These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of DeltaFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in DeltaFosB and RGS9 occur in humans with Parkinson's disease. Knowledge of these adaptations can help us understand the changes in striatal function associated with Parkinson's disease and assist in the development of novel treatments.
Authors: Lisa F Potts; Eun S Park; Jong-Min Woo; Bhagya L Dyavar Shetty; Arun Singh; Steven P Braithwaite; Michael Voronkov; Stella M Papa; M Maral Mouradian Journal: Ann Neurol Date: 2015-03-27 Impact factor: 10.422
Authors: Zili Luo; Katelin E Ahlers-Dannen; Mackenzie M Spicer; Jianqi Yang; Stephanie Alberico; Hanna E Stevens; Nandakumar S Narayanan; Rory A Fisher Journal: JCI Insight Date: 2019-05-23
Authors: Haili Zhang; Ming Zheng; Manhong Wu; Dan Xu; Toshihiko Nishimura; Yuki Nishimura; Rona Giffard; Xiaoxing Xiong; Li Jun Xu; J David Clark; Peyman Sahbaie; David L Dill; Gary Peltz Journal: Genetics Date: 2016-03-18 Impact factor: 4.562
Authors: Anna J Jasinska; Susan Service; Oi-wa Choi; Joseph DeYoung; Olivera Grujic; Sit-yee Kong; Matthew J Jorgensen; Julia Bailey; Sherry Breidenthal; Lynn A Fairbanks; Roger P Woods; J David Jentsch; Nelson B Freimer Journal: Hum Mol Genet Date: 2009-08-19 Impact factor: 6.150