Kitamoto T, Tateishi J
Department of Neuropathology, Kyushu University, Fukuoka, Japan.
Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):391-8. doi: 10.1098/rstb.1994.0034.
Recent molecular genetic studies revealed that the human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to a distinct type of prion diseases. We report herein that it is useful to classify prion diseases into plaque type or non-plaque type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 105, codon 129, codon 145 and insertional polymorphisms belong to the plaque type prion diseases, whereas the wild-type PrP and the variants including codon 180, codon 200, and codon 232 polymorphisms belong to the non-plaque type. The non-plaque type prion diseases showed a rapidly progressive dementia, myoclonus and periodic synchronous discharges in the electroencephalogram, and in the pathological findings diffuse grey matter PrP accumulations including the synaptic structures. The plaque type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposits in the central nervous system influences the clinical and pathological aspects of prion diseases. Thus, PrP accumulations may play a central role in the pathogenesis of prion diseases.
最近的分子遗传学研究表明，人类朊病毒蛋白（PrP）基因具有大量的多态性和突变。每种变异型PrP似乎都对应于一种独特类型的朊病毒疾病。我们在此报告，根据PrP在中枢神经系统中的分布将朊病毒疾病分为斑块型或非斑块型是有用的。包括密码子102、密码子105、密码子129、密码子145和插入多态性的变异型PrP属于斑块型朊病毒疾病，而野生型PrP以及包括密码子180、密码子200和密码子232多态性的变异型属于非斑块型。非斑块型朊病毒疾病表现为快速进展性痴呆、肌阵挛和脑电图中的周期性同步放电，并且在病理检查中可见包括突触结构在内的弥漫性灰质PrP积聚。斑块型朊病毒疾病临床病程较长，无肌阵挛和周期性同步放电，主要的PrP积聚部位是细胞外PrP斑块。PrP在中枢神经系统中的沉积分布影响朊病毒疾病的临床和病理表现。因此，PrP积聚可能在朊病毒疾病的发病机制中起核心作用。
