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Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target

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Book cover Therapeutic Applications of Dopamine D3 Receptor Function

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 60))

Abstract

Parkinson disease (PD) dementia, pathologically featured as nigrostriatal dopamine (DA) neuronal loss with motor and non-motor manifestations, leads to substantial disability and economic burden. DA therapy targets the DA D3 receptor (D3R) with high affinity and selectivity. The pathological involvement of D3R is evidenced as an effective biomarker for disease progression and DA agnostic interventions, with compensations of increased DA, decreased aggregates of α-synuclein (α-Syn), enhanced secretion of brain-derived neurotrophic factors (BDNF), attenuation of neuroinflammation and oxidative damage, and promoting neurogenesis in the brain. D3R also interacts with D1R to reduce PD-associated motor symptoms and alleviate the side effects of levodopa (L-DOPA) treatment. We recently found that DA D2 receptor (D2R) density decreases in the late-stage PDs, while high D3R or DA D1 receptor (D1R) + D3R densities in the postmortem PD brains correlate with survival advantages. These new essential findings warrant renewed investigations into the understanding of D3R neuron populations and their cross-sectional and longitudinal regulations in PD progression.

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Acknowledgments

Thanks to Mr. William Knight and Dr. Pengfei Yang for editorial assistance and the funding support from the National Institutes of Health (R01 NS092865).

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  1. Division of Radiological Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Jinbin Xu

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  1. Addiction Imaging Research Group, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Isabelle Boileau

  2. Dept of Molecular&Translational Medicine, University of Brescia, Brescia, Italy

    Ginetta Collo

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Xu, J. (2022). Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target. In: Boileau, I., Collo, G. (eds) Therapeutic Applications of Dopamine D3 Receptor Function. Current Topics in Behavioral Neurosciences, vol 60. Springer, Cham. https://doi.org/10.1007/7854_2022_373

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