Division of Radiological Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Curr Top Behav Neurosci. 2023;60:89-107. doi: 10.1007/7854_2022_373.
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.
帕金森病（PD）痴呆，其病理特征为黑质纹状体多巴胺（DA）神经元丧失，伴有运动和非运动表现，导致严重残疾和经济负担。DA 治疗的靶点是具有高亲和力和选择性的 DA D3 受体（D3R）。D3R 的病理性参与被证明是疾病进展和 DA 不可知干预的有效生物标志物，其补偿作用包括增加 DA、减少 α-突触核蛋白（α-Syn）的聚集、增强脑源性神经营养因子（BDNF）的分泌、减轻神经炎症和氧化损伤，以及促进大脑中的神经发生。D3R 还与 D1R 相互作用，以减轻与 PD 相关的运动症状，并减轻左旋多巴（L-DOPA）治疗的副作用。我们最近发现，在晚期 PD 中，DA D2 受体（D2R）密度降低，而在 PD 死后大脑中高 D3R 或 DA D1 受体（D1R）+D3R 密度与生存优势相关。这些新的重要发现需要重新研究 D3R 神经元群体及其在 PD 进展中的横断面和纵向调节。
