丝氨酸蛋白酶HtrA1在淀粉样前体蛋白加工过程中的影响。
Implications of the serine protease HtrA1 in amyloid precursor protein processing.
作者信息
Grau Sandra, Baldi Alfonso, Bussani Rossana, Tian Xiaodan, Stefanescu Raluca, Przybylski Michael, Richards Peter, Jones Simon A, Shridhar Viji, Clausen Tim, Ehrmann Michael
机构信息
School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6021-6. doi: 10.1073/pnas.0501823102.
Abstract
The defining features of the widely conserved HtrA (high temperature requirement) family of serine proteases are the combination of a catalytic protease domain with one or more C-terminal PDZ domains and reversible zymogen activation. Even though HtrAs have previously been implicated in protein quality control and various diseases, including cancer, arthritis, and neuromuscular disorder, the biology of the human family members is not well understood. Our data suggest that HtrA1 is directly involved in the beta-amyloid pathway as it degrades various fragments of amyloid precursor protein while an HtrA1 inhibitor causes accumulation of Abeta in astrocyte cell culture supernatants. Furthermore, HtrA1 colocalizes with beta-amyloid deposits in human brain samples. Potential implications in Alzheimer's disease are discussed.
摘要
丝氨酸蛋白酶的HtrA（高温需求）家族广泛保守，其决定性特征是催化蛋白酶结构域与一个或多个C端PDZ结构域相结合以及酶原的可逆激活。尽管此前已有研究表明HtrA参与蛋白质质量控制以及包括癌症、关节炎和神经肌肉疾病在内的多种疾病，但人们对人类家族成员的生物学特性仍了解不足。我们的数据表明，HtrA1直接参与β-淀粉样蛋白途径，因为它能降解淀粉样前体蛋白的各种片段，而HtrA1抑制剂会导致星形胶质细胞培养上清液中Aβ的积累。此外，HtrA1与人脑样本中的β-淀粉样蛋白沉积物共定位。文中还讨论了其在阿尔茨海默病中的潜在意义。
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