Matsumine H
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
J Neurol. 1998 Nov;245(11 Suppl 3):P10-4. doi: 10.1007/pl00007741.
We present a genetic model of selective nigral neuron death without Lewy body formation--autosomal recessive juvenile parkinsonism (AR-JP). Mapping of AR-JP gene to a single recessive locus on chromosome 6q25.2-27 is a strong indication of the idea that a loss-of-function mutation of a single gene is sufficient to cause selective nigral neuron death. The absence of Lewy body formation in AR-JP is important, because most cases of neuron death caused by loss-of-function mechanism are not accompanied by inclusion body. Our findings clearly indicate that nigral cells are critically dependent for their survival on the function of AR-JP protein. This raises an important question of whether or not AR-JP protein contributes to the downstream pathway of cell death in Parkinson's disease.
我们提出了一种无路易小体形成的选择性黑质神经元死亡的遗传模型——常染色体隐性青少年帕金森病（AR-JP）。将AR-JP基因定位到6号染色体q25.2-27上的一个单一隐性位点，有力地表明了单个基因功能丧失突变足以导致选择性黑质神经元死亡这一观点。AR-JP中不存在路易小体形成很重要，因为大多数由功能丧失机制导致的神经元死亡病例都不伴有包涵体。我们的研究结果清楚地表明，黑质细胞的存活严重依赖于AR-JP蛋白的功能。这就引出了一个重要问题，即AR-JP蛋白是否在帕金森病细胞死亡的下游通路中发挥作用。
