In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant enzyme protein with abnormal steric structure that is expressed by gene mutation. Chaperone therapy is a new molecular therapeutic approach primarily for lysosomal diseases. The misfolded mutant enzyme is digested rapidly or aggregated to induce endoplasmic reticulum stress. As a result, the catalytic activity is lost. The following sequence of events are follows the chaperone therapy to achieve correction of molecular pathology. An orally administered low molecular competitive inhibitor (chaperone) is absorbed into the bloodstream and reaches the target cells and tissues. The mutant enzyme is stabilized by the chaperone and subjected to normal enzyme proteinfolding (proteostasis). The first chaperone drug was developed for Fabry disease and is currently available in medical practice. At present three types of chaperones are available: competitive chaperone with enzyme inhibitory bioactivity (exogenous), non-competitive (or allosteric) chaperone without inhibitory bioactivity (exogenous), and molecular chaperone (heat shock protein; endogenous). The third endogenous chaperone would be directed to overexpression or activated by an exogenous low-molecular inducer. This new molecular therapeutic approach, utilizing the three types of chaperone, is expected to apply to a variety of diseases, genetic or non-genetic, and neurological or non-neurological, in addition to lysosomal diseases.

中文翻译：

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溶酶体疾病分子病理学的伴侣疗法

在溶酶体疾病中，酶缺乏是由基因突变表达的具有异常空间结构的突变酶蛋白错误折叠引起的。分子伴侣疗法是一种新的分子治疗方法，主要用于溶酶体疾病。错误折叠的突变酶被快速消化或聚集以诱导内质网应激。结果，催化活性丧失。以下事件序列遵循伴侣疗法以实现分子病理学的校正。口服的低分子竞争性抑制剂（分子伴侣）被吸收到血流中并到达靶细胞和组织。突变酶由分子伴侣稳定并进行正常的酶蛋白折叠（蛋白质稳态）。第一种伴侣药物是为法布里病开发的，目前可用于医疗实践。目前有三种类型的分子伴侣：具有酶抑制生物活性的竞争性分子伴侣（外源性）、无抑制性生物活性的非竞争性（或变构）分子伴侣（外源性）和分子伴侣（热休克蛋白；内源性）。第三个内源性伴侣将被导向过度表达或被外源性低分子诱导剂激活。除了溶酶体疾病外，这种利用三种分子伴侣的新分子治疗方法有望应用于遗传或非遗传、神经或非神经疾病等多种疾病。没有抑制性生物活性的非竞争性（或变构）分子伴侣（外源性）和分子伴侣（热休克蛋白；内源性）。第三个内源性伴侣将被导向过度表达或被外源性低分子诱导剂激活。除了溶酶体疾病外，这种利用三种分子伴侣的新分子治疗方法有望应用于遗传或非遗传、神经或非神经疾病等多种疾病。没有抑制性生物活性的非竞争性（或变构）分子伴侣（外源性）和分子伴侣（热休克蛋白；内源性）。第三个内源性伴侣将被导向过度表达或被外源性低分子诱导剂激活。除了溶酶体疾病外，这种利用三种分子伴侣的新分子治疗方法有望应用于遗传或非遗传、神经或非神经疾病等多种疾病。