Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA.
Mol Genet Metab. 2010 Dec;101(4):307-10. doi: 10.1016/j.ymgme.2010.08.004. Epub 2010 Aug 10.
Mutant GBA was found recently to be the most prevalent risk factor for familial parkinsonism. The two diseases do not share common symptoms and there is no direct pathway to explain the mechanism by which GBA mutations can confer the risk. Increased burden on the degradative pathway caused by defective glucocerebrosidase, or toxic side effects of glycosylated lipids accumulation were proposed to explain brain damage. Both hypotheses are not sufficient to explain the linkage. In order to develop a more inclusive theory we introduced into the model the prion theory and the second hit. Other possibilities are also brought into consideration.
最近发现，突变 GBA 是家族性帕金森病最常见的风险因素。这两种疾病没有共同的症状，也没有直接的途径可以解释 GBA 突变如何带来风险。有人提出，葡萄糖脑苷脂酶缺陷导致降解途径负担增加，或糖基化脂质积累的毒性副作用，可能导致大脑损伤。这两种假说都不足以解释这种关联。为了提出一个更具包容性的理论，我们将朊病毒理论和二次打击引入到模型中。同时也考虑了其他可能性。
