Altered regulation of serum lysosomal acid hydrolase activities in Parkinson's disease: A potential peripheral biomarker?
Altered regulation of serum lysosomal acid hydrolase activities in Parkinson's disease: A potential peripheral biomarker?
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DOI：
10.1016/j.parkreldis.2018.10.032
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发表时间：
2019-04-01
影响因子：
4.1
通讯作者：
Mutoh, Tatsuro
中科院分区：
文献类型：
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作者：
Niimi, Yoshiki;Ito, Shinji;Mutoh, Tatsuro
引言：最近的研究表明，溶酶体功能障碍有助于特发性帕金森病（PD）的发展。目前尚不清楚是否存在血清溶酶体酸水解酶活性失调的散发性PD患者与正常对照组（NC）和帕金森综合征（PS）patients.Methods：散发性PD患者无GBA 1突变（n = 68）与正常对照组（n = 45），帕金森综合征患者（n = 32）的家族史，年龄和性别相匹配。我们测量了溶酶体酶、α-半乳糖苷酶、β-半乳糖苷酶和β-氨基己糖苷酶的活性，并研究了溶酶体酸水解酶活性与NC、PD和PS患者年龄之间的可能相关性。β-半乳糖苷酶/α-半乳糖苷酶和β-氨基己糖苷酶/β-半乳糖苷酶活性比值更有助于区分PD和PS患者与NC（P < 0.0001）。此外，PS患者的α-半乳糖苷酶活性显著高于PD和NC组（p = 0.04）。NC中β-半乳糖苷酶和α-半乳糖苷酶活性与年龄呈显著负相关，PS中β-氨基己糖苷酶活性与年龄呈正相关。然而，PD患者并未表现出任何这些相关性。结论：我们的研究结果表明，正常人群中血清酸水解酶活性随着年龄的增长存在未知的调节机制，而PD和PS患者的血清酸水解酶活性调节异常。然而，这两组的失调模式是不同的。因此，血清溶酶体酸水解酶活性可用作PD的外周生物标志物。
Introduction: Recent studies have indicated that lysosomal dysfunction contributes to the development of idiopathic Parkinson's disease (PD). It is uncertain whether dysregulation of serum lysosomal acid hydrolase activity exists in sporadic PD patients compared with normal controls (NCs) and parkinsonian syndrome (PS) patients.Methods: Sporadic PD patients without GBA1 mutations (n = 68) were matched with normal controls (n = 45), and parkinsonian syndrome patients (n = 32) in terms of family history, age, and sex. We measured the activities of lysosomal enzymes, alpha-galactosidase, beta-galactosidase, and beta-hexosaminidase and examined the possible correlations between lysosomal acid hydrolase activities with age in NCs, PD, and PS patients.Results: beta-Galactosidase activity was significantly higher in the PD and PS than in the NC group (P < 0.001). The beta-galactosidase to alpha-galactosidase and beta-hexosaminidase to beta-galactosidase activity ratios were more useful for distinguishing PD and PS patients from NCs (P < 0.0001). Furthermore, alpha-galactosidase activity was significantly higher in PS patients than both PD and NC groups (p = 0.04). beta-Galactosidase and alpha-galactosidase activities exhibited a statistically significant negative correlation with age in NCs, and beta-hexosaminidase activity showed a positive correlation with age in PS. However, PD patients did not show any of these correlations.Conclusion: Our results suggest the presence of an unknown regulatory mechanism(s) of serum acid hydrolase activities with aging in the normal population and abnormalities in their regulation in PD and PS patients. However, the pattern of dysregulation in these two groups is different. Thus, serum lysosomal acid hydrolase activity can be used as a peripheral biomarker for PD.