Li Yaqiong, Li Ping, Liang Huimin, Zhao Zhiquan, Hashimoto Makoto, Wei Jianshe
Laboratory of Brain Function and Disease, Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng, 475004, China.
Cell Mol Neurobiol. 2015 Aug;35(6):755-61. doi: 10.1007/s10571-015-0176-8. Epub 2015 Mar 29.
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.
戈谢病与帕金森病（PD）通过葡糖脑苷脂酶（GCase）的突变相关联。编码GCase的基因，即β-葡萄糖苷酶酸（GBA），是PD的一个重要风险因素。大型研究的结果表明，PD患者中GBA突变的频率增加，并且GBA突变携带者表现出多样的帕金森病表型和路易小体病理。尽管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突变导致的功能获得，这增加了α-突触核蛋白（α-syn）的聚集，溶酶体酶缺乏导致的功能丧失，这影响了α-syn的清除，甚至还有一个双向反馈环，但这些假说中的每一个都有其局限性。还值得注意的是，许多研究结果都涉及α-syn与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至关重要的作用。因此，本综述聚焦于α-syn和GCase，并提供了一些新的思路，可能有助于理解α-syn-GCase相互作用并阐明GBA相关帕金森综合征的确切机制。
