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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders.
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Neurosecretases provide strategies to treat sporadic and familial Alzheimer disorders.

机译：神经分泌酶提供了治疗散发性和家族性阿尔茨海默氏病的策略。

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摘要

Recent discoveries on neurosecretases and their trafficking to release fibril-forming neuropeptides or other products, are of interest to pathology, cell signaling and drug discovery. Nomenclature arose from the use of amyloid precursor protein (APP) as a prototypic type-1 substrate leading to the isolation of beta-secretase (BACE), multimeric complexes (gamma-secretase, gamma-SC) for intramembranal cleavage, and attributing a new function to well-characterized metalloproteases of the ADAM family (alpha-secretase) for normal APP turnover. While purified alpha/beta-secretases facilitate drug discovery, gamma-SC presents greater challenges for characterization and mechanisms of catalysis. The review comments on links between mutation or polymorphisms in relation to enzyme mechanisms and disease. The association between lipoprotein receptor LRP11 variants and sporadic Alzheimer's disease (SAD) offers scope to integrate components of pre- and post-Golgi membranes, or brain clathrin-coated vesicles within pathways for trafficking as targets for intervention. The presence of APP and metabolites in brain clathrin-coated vesicles as significant cargo with lipoproteins and adaptors focuses attention as targets for therapeutic intervention. This overview emphasizes the importance to develop new therapies targeting neurosecretases to treat a major neurological disorder that has vast economic and social implications.
机译：关于神经分泌酶及其转运以释放原纤维形成的神经肽或其他产物的最新发现，对病理学，细胞信号转导和药物发现很感兴趣。由于使用淀粉样蛋白前体蛋白（APP）作为原型1型底物而产生了命名法，从而导致β-分泌酶（BACE），多聚体复合物（γ-分泌酶，γ-SC）的分离用于膜内裂解，并归因于一种新的对于正常的APP营业额，其功能对ADAM家族的特征明确的金属蛋白酶（α-分泌酶）有效。尽管纯化的α/β-分泌酶有助于药物发现，但γ-SC在表征和催化机理方面提出了更大的挑战。该评论评论了与酶机制和疾病有关的突变或多态性之间的联系。脂蛋白受体LRP11变体与偶发性阿尔茨海默氏病（SAD）之间的关联提供了将高尔基体前膜和后膜或脑网格蛋白包被的囊泡的成分整合到贩运途径中作为干预目标的范围。在脑网格蛋白包被的囊泡中，APP和代谢物以脂蛋白和衔接子的形式大量存在，引起人们的关注，成为治疗干预的目标。该概述强调开发针对神经分泌酶的新疗法以治疗具有广泛的经济和社会意义的主要神经系统疾病的重要性。

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