Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target.
Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target.
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DOI：
10.1007/7854_2022_373
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发表时间：
2023
影响因子：
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通讯作者：
Xu, Jinbin
中科院分区：
文献类型：
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作者：
Xu, Jinbin
帕金森病（Parkinson disease，PD）痴呆是一种以黑质纹状体多巴胺（dopamine，DA）神经元丢失为主要病理特征的运动和非运动性痴呆，可导致严重的残疾和经济负担。DA疗法以高亲和力和选择性靶向DA D3受体（D3 R）。D3 R的病理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，具有增加的DA、减少的α-突触核蛋白（α-Syn）聚集体、增强的脑源性神经营养因子（BDNF）分泌、减轻神经炎症和氧化损伤以及促进脑中神经发生的补偿作用。D3 R还与D1 R相互作用，以减少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，DA D2受体（D2 R）密度在晚期PD中降低，而死后PD脑中的高D3 R或DA D1受体（D1 R）+D3 R密度与生存优势相关。这些新的重要发现保证了对D3 R神经元群体及其在PD进展中的横截面和纵向调节的理解的重新调查。
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.