Oasi Research Institute-IRCCS, Troina, EN, Italy.
Fondazione Grigioni per il Morbo di Parkinson, via Zuretti 35, I-20135, Milan, Italy.
Neurochem Int. 2021 Mar;144:104978. doi: 10.1016/j.neuint.2021.104978. Epub 2021 Jan 29.
Poly (ADP-ribose) polymerase 1 (PARP1) is crucial in both maintenance of genome integrity and cell death. PARP1 activation has been very recently linked to Parkinson's disease (PD) and its role in inducing the pathologic accumulation of α-Synuclein demonstrated in a PD mouse model. The objective of this study was to investigate the presence and localization of PARP1 in PD brain. PARP1 localization was assessed by immunostaining and confocal microscopy in post-mortem human brains obtained from PD patients (Braak stage VI) compared to controls. PARP1 positive nuclei in substantia nigra, mainly in dopaminergic neurons but also in astrocytes and oligodendrocytes, were decreased in PD. The same alteration was observed in several areas that are affected in PD pathology, namely the dorsal motor nucleus of vagus, frontal and cingulate cortex, whereas no changes in PARP1 staining were detectable in the inferior olivary nucleus that is unaffected in PD. In addition, PARP1 co-localizes with α-Synuclein that is accumulated in the cytoplasm and in Lewy bodies of PD tissue sections. Our data reveal previously unknown changes of PARP1 localization in the brain of PD patients, in both neurons and glia, supporting its widespread involvement in this pathology and its potential use as a therapeutic target.
聚（ADP-核糖）聚合酶 1（PARP1）在维持基因组完整性和细胞死亡中都至关重要。PARP1 的激活最近与帕金森病（PD）有关，并且在 PD 小鼠模型中证明了其诱导α-突触核蛋白病理性积累的作用。本研究的目的是研究 PARP1 在 PD 脑中的存在和定位。通过免疫染色和共聚焦显微镜评估 PARP1 在死后人类大脑中的定位，这些大脑取自 PD 患者（Braak 阶段 VI）与对照组相比。黑质中 PARP1 阳性核，主要是多巴胺能神经元，但也存在于星形胶质细胞和少突胶质细胞中，在 PD 中减少。在 PD 病理学中受影响的几个区域也观察到了相同的改变，即迷走神经背核、额皮质和扣带皮质，而在 PD 中不受影响的下橄榄核中则没有检测到 PARP1 染色的改变。此外，PARP1 与α-突触核蛋白共定位，α-突触核蛋白在 PD 组织切片的细胞质和路易小体中积累。我们的数据揭示了 PD 患者大脑中 PARP1 定位的先前未知变化，包括神经元和神经胶质细胞，支持其在该病理学中的广泛参与及其作为治疗靶点的潜在用途。
