Sideras Kostandinos, Gertz Morie A
Division of Hematology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Adv Clin Chem. 2009;47:1-44.
Amyloidosis is a heterogeneous group of diseases in which an otherwise normal protein, with or without proteolytic cleavage, forms insoluble amyloid fibrils. These, in turn, deposit in various organs and cause dysfunction. A wide range of diseases are associated with amyloidosis such as Alzheimer's disease, multiple myeloma, other plasma cell disorders, and chronic inflammation, either as a cause, or result, of amyloid production. This heterogeneity in cause and presentation leads to an incomplete understanding of the pathophysiology of amyloid disease. As such, study of this complicated disease process presents significant challenges. The purpose of this review article is to introduce the biochemistry of amyloidosis including ultrastructure analysis, models of monomer aggregation, the importance of the amyloid microenvironment, and the mechanisms of organ dysfunction, including the role of "toxic intermediates." Pathophysiologic analysis of amyloidosis will focus on diagnostic tools as well as the classification of the various forms of amyloidosis. Finally, treatment of amyloidosis will be reviewed including traditional and established modalities. We will also introduce new and novel treatment options as they relate to the basic pathophysiology of this complex and heterogeneous disorder.
淀粉样变是一组异质性疾病，在这些疾病中，一种原本正常的蛋白质，无论有无蛋白水解切割，都会形成不溶性淀粉样纤维。这些纤维进而沉积在各种器官中并导致功能障碍。多种疾病与淀粉样变相关，如阿尔茨海默病、多发性骨髓瘤、其他浆细胞疾病以及慢性炎症，它们或是淀粉样蛋白产生的原因，或是结果。病因和表现的这种异质性导致对淀粉样疾病病理生理学的理解不完整。因此，对这个复杂疾病过程的研究面临重大挑战。这篇综述文章的目的是介绍淀粉样变的生物化学，包括超微结构分析、单体聚集模型、淀粉样微环境的重要性以及器官功能障碍的机制，包括“毒性中间体”的作用。淀粉样变的病理生理学分析将侧重于诊断工具以及各种淀粉样变形式的分类。最后，将回顾淀粉样变的治疗方法，包括传统的和已确立的治疗方式。我们还将介绍与这种复杂异质性疾病的基本病理生理学相关的新的和新颖的治疗选择。
