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[神经病理学]

[Neuropathology].

作者信息

Saito Yuko, Murayama Shigeo

机构信息

Department of Pathology and Laboratory Medicine, National Center Hospital of Neurology and Psychiatry.

出版信息

Rinsho Shinkeigaku. 2011 Nov;51(11):1168-71. doi: 10.5692/clinicalneurol.51.1168.

Abstract

This research is based on the brain bank project, which combines prospective clinical follow ups and retrospective neuropathological studies. Pathology of idiopathic Parkinson disease (PD) can be summarized as a spectrum of Lewy body (LB) disease (LBD) comprising PD, dementia with LB (DLB) and pure autonomic failure (PAF). Recently core protein component of LB is proved to be alpha-synuclein, which is truncated, phosphorylated and ubiquitinated. Immunohistochemistry with anti-phosphorylated alpha-synuclein (psyn) antibody visualizes LB pathology with previously unattained high sensitivity and specificity, and enables pathological studies of peripheral autonomic nervous system as well as central nervous system. Recently Braak et al proposed ascending extension hypothesis of LB pathology, based on consecutive autopsy cases of PD and normal controls without dementia. However, not excluding demented cases, we found olfactory-amygdala extension pathway of LB pathology, which is independent from Braak's ascending pathway. We propose that abnormal seeding and aggregation of alpha-synuclein could be formed in peripheral autonomic nervous system or olfactory bulb and extend via neural network and form clinical phenotype of LBD.

摘要

本研究基于脑库项目,该项目结合了前瞻性临床随访和回顾性神经病理学研究。特发性帕金森病(PD)的病理学可概括为路易体(LB)病(LBD)的一个谱系,包括PD、路易体痴呆(DLB)和单纯自主神经功能衰竭(PAF)。最近,LB的核心蛋白成分被证明是α-突触核蛋白,它被截断、磷酸化和泛素化。用抗磷酸化α-突触核蛋白(psyn)抗体进行免疫组织化学可以前所未有的高灵敏度和特异性显示LB病理学,并能够对外周自主神经系统以及中枢神经系统进行病理学研究。最近,Braak等人基于PD连续尸检病例和无痴呆的正常对照提出了LB病理学的上升扩展假说。然而,在不排除痴呆病例的情况下,我们发现了LB病理学的嗅觉-杏仁核扩展途径,它独立于Braak的上升途径。我们提出,α-突触核蛋白的异常播种和聚集可能在外周自主神经系统或嗅球中形成,并通过神经网络扩展,形成LBD的临床表型。

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