Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-0811, Japan.
Neurochem Int. 2022 May;155:105313. doi: 10.1016/j.neuint.2022.105313. Epub 2022 Feb 23.
Transthyretin (TTR), which is one of the major amyloidogenic proteins in systemic amyloidosis, forms extracellular amyloid deposits in the systemic organs such as nerves, ligaments, heart, and arterioles, and causes two kinds of systemic amyloidosis, hereditary ATTR (ATTRv) amyloidosis induced by variant TTR and aging-related wild-type ATTR (ATTRwt) amyloidosis. More than 150 different mutations, most of which are amyloidogenic, have been reported in the TTR gene. Since most disease-associated mutations affect TTR tetramer dissociation rates, destabilization of TTR tetramers is widely believed to be a critical step in TTR amyloid formation. Recently, effective disease-modifying therapies such as TTR tetramer stabilizers and TTR gene silencing therapies have been developed for ATTR amyloidosis. This study reviews the clinical phenotypes of ATTR amyloidosis, TTR features, and recent progress in promising therapies for ATTR amyloidosis.
转甲状腺素蛋白（TTR）是全身性淀粉样变性症中主要的淀粉样蛋白之一，在神经、韧带、心脏和小动脉等全身器官中形成细胞外淀粉样沉积物，导致两种全身性淀粉样变性症，即由变异 TTR 引起的遗传性 ATTR（ATTRv）淀粉样变性症和与年龄相关的野生型 ATTR（ATTRwt）淀粉样变性症。在 TTR 基因中已报道了超过 150 种不同的突变，其中大多数为淀粉样变性。由于大多数与疾病相关的突变会影响 TTR 四聚体解离速率，因此 TTR 四聚体的不稳定性被广泛认为是 TTR 淀粉样形成的关键步骤。最近，已经开发出了有效的疾病修饰疗法，如 TTR 四聚体稳定剂和 TTR 基因沉默疗法，用于治疗 ATTR 淀粉样变性症。本研究综述了 ATTR 淀粉样变性症的临床表型、TTR 特征以及治疗 ATTR 淀粉样变性症的有前途疗法的最新进展。
