Gaucher-Associated Parkinsonism.
Gaucher-Associated Parkinsonism.
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戈谢相关帕金森病
DOI：
10.1007/s10571-015-0176-8
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发表时间：
2015-08
影响因子：
4
通讯作者：
Wei J
中科院分区：
文献类型：
--
作者：
Li Y;Li P;Liang H;Zhao Z;Hashimoto M;Wei J
戈谢病与帕金森病（PD）通过葡萄糖脑苷脂酶（GCase）突变相关。编码GCase的基因，葡萄糖苷酶β酸（GBA），是PD的重要危险因素。大型研究的结果表明，PD患者GBA突变频率增加，GBA突变携带者表现出不同的帕金森病表型和路易体病理。虽然这种关联的机制仍然难以捉摸，但已经提出了一些假说来解释它，包括GBA突变引起的功能获得，这增加了α-突触核蛋白（α-syn）聚集，由于溶酶体酶缺乏引起的功能丧失，这影响了α-syn清除，甚至是双向反馈回路，但这些假说都有其局限性。同样值得注意的是，许多研究结果表明α-syn和GCase之间的相互作用，表明这种相互作用在GBA相关帕金森综合征的发病机制中起着重要作用。本文就α-syn与GCase的相互作用进行综述，为进一步了解α-syn与GCase的相互作用及GBA相关性帕金森病的发病机制提供新的思路。
Gaucher disease is associated with Parkinson’s disease (PD) by mutations in glucocerebrosidase (GCase). The gene encoding GCase, glucosidase beta acid (GBA), is an important risk factor for PD. Findings from large studies have shown that patients with PD have an increased frequency of mutations in GBA and that GBA mutation carriers exhibit diverse parkinsonian phenotypes and Lewy body pathology. Although the mechanism for this association remains elusive, some hypotheses have been proposed to explain it, including gain of function caused by GBA mutations, which increases α-synuclein (α-syn) aggregation, loss of function due to lysosomal enzyme deficiency, which affects α-syn clearance, and even a bidirectional feedback loop, but each of these hypotheses has its limitations. It is also worth noting that many findings have implicated the interaction between α-syn and GCase, indicating the essential role of the interaction in the pathogenesis of GBA-associated parkinsonism. Therefore, the current review focuses on α-syn and GCase, and it provides some new thoughts that may be helpful for understanding the α-syn-GCase interaction and unraveling the exact mechanism underlying GBA-associated parkinsonism.