Department of Neurology, Goethe University, Frankfurt/Main, Germany.
BMC Neurol. 2011 Jun 20;11:74. doi: 10.1186/1471-2377-11-74.
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and α-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system.
It has recently been found that α-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of α-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities.
At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities.
帕金森病（PD）是一种缓慢进展的神经退行性疾病，影响脑干、基底神经节和大脑皮层的广泛区域。已知许多蛋白质在帕金森病脑中积累，包括泛素和α-突触核蛋白。朊病毒病是由朊病毒蛋白作为传染性蛋白颗粒通过脑组织传播错误折叠蛋白构象引起的散发性、遗传性或传染性疾病，具有各种临床和组织病理学特征。最重要的形式是克雅氏病，它与朊病毒蛋白的自我传播病理前体形式有关，该蛋白在中枢神经系统中广泛分布。
最近发现，α-突触核蛋白可能表现得类似于朊病毒前体，并在细胞间传播。在 PD 患者的胚胎多巴胺细胞移植中含有路易体的α-突触核蛋白的死后证明表明，错误折叠的蛋白可能从患病宿主传播到供体神经元，类似于朊病毒的行为。基底神经节和脑干在退行性过程中的参与是帕金森病和克雅氏病之间的其他一致性。然而，在将帕金森病归类为朊病毒疾病之前，有许多问题需要谨慎，因为这两种疾病实体的临床表现、脑成像、脑脊液和神经病理学发现存在根本差异。最重要的是，传染性是朊病毒疾病的一个关键特征，迄今为止在 PD 中从未观察到。此外，朊病毒蛋白的细胞传播尚未明确界定，因此难以评估这两种疾病实体之间的分子相似性。
在目前的知识状态下，传染性致病蛋白的分子途径尚未完全了解。为了阐明这两种目前被认为是不同实体的疾病类别之间可能存在的重叠，需要进一步研究它们在朊病毒疾病和神经退行性疾病的病理生理学中的确切参与。
