Martínez-Bailén Macarena, Clemente Francesca, Matassini Camilla, Cardona Francesca
Dipartimento di Chimica "Ugo Schiff" (DICUS), Università degli Studi di Firenze, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy.
Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Av. Américo Vespucio 49, 41092 Sevilla, Spain.
Pharmaceuticals (Basel). 2022 Jul 2;15(7):823. doi: 10.3390/ph15070823.
Pharmaceutical chaperones (PCs) are small compounds able to bind and stabilize misfolded proteins, allowing them to recover their native folding and thus their biological activity. In particular, lysosomal storage disorders (LSDs), a class of metabolic disorders due to genetic mutations that result in misfolded lysosomal enzymes, can strongly benefit from the use of PCs able to facilitate their translocation to the lysosomes. This results in a recovery of their catalytic activity. No PC for the GCase enzyme (lysosomal acid-β-glucosidase, or glucocerebrosidase) has reached the market yet, despite the importance of this enzyme not only for Gaucher disease, the most common LSD, but also for neurological disorders, such as Parkinson's disease. This review aims to describe the efforts made by the scientific community in the last 7 years (since 2015) in order to identify new PCs for the GCase enzyme, which have been mainly identified among glycomimetic-based compounds.
药物伴侣（PCs）是一类能够结合并稳定错误折叠蛋白质的小分子化合物，可使其恢复天然折叠状态并进而恢复生物学活性。特别是溶酶体贮积症（LSDs），这是一类由于基因突变导致溶酶体酶错误折叠的代谢紊乱疾病，使用能够促进其转运至溶酶体的PCs可使其受益匪浅。这会使其催化活性得以恢复。尽管葡糖脑苷脂酶（GCase酶，即溶酶体酸性β-葡萄糖苷酶，或葡萄糖脑苷脂酶）不仅对最常见的LSD——戈谢病很重要，而且对帕金森病等神经疾病也很重要，但目前尚无用于该酶的PCs上市。本综述旨在描述科学界在过去7年（自2015年以来）为鉴定GCase酶的新型PCs所做的努力，这些PCs主要是在基于糖模拟物的化合物中鉴定出来的。
