Transthyretin (TTR) amyloidoses are systemic diseases associated with TTR aggregation and extracellular deposition in tissues as amyloid. The most frequent and severe forms of the disease are hereditary and associated with amino acid substitutions in the protein due to single point mutations in the TTR gene (ATTRv amyloidosis). However, the wild type TTR (TTR wt) has an intrinsic amyloidogenic potential that, in particular altered physiologic conditions and aging, leads to TTR aggregation in people over 80 years old being responsible for the non-hereditary ATTRwt amyloidosis. In normal physiologic conditions TTR wt occurs as a tetramer of identical subunits forming a central hydrophobic channel where small molecules can bind as is the case of the natural ligand thyroxine (T₄). However, the TTR amyloidogenic variants present decreased stability, and in particular conditions, dissociate into partially misfolded monomers that aggregate and polymerize as amyloid fibrils. Therefore, therapeutic strategies for these amyloidoses may target different steps in the disease process such as decrease of variant TTR (TTRv) in plasma, stabilization of TTR, inhibition of TTR aggregation and polymerization or disruption of the preformed fibrils. While strategies aiming decrease of the mutated TTR involve mainly genetic approaches, either by liver transplant or the more recent technologies using specific oligonucleotides or silencing RNA, the other steps of the amyloidogenic cascade might be impaired by pharmacologic compounds, namely, TTR stabilizers, inhibitors of aggregation and amyloid disruptors. Modulation of different steps involved in the mechanism of ATTR amyloidosis and compounds proposed as pharmacologic agents to treat TTR amyloidosis will be reviewed and discussed.

运甲状腺素蛋白（TTR）淀粉样蛋白是与TTR聚集和淀粉样蛋白在组织中的细胞外沉积有关的系统性疾病。该疾病最常见和最严重的形式是遗传性的，并且由于蛋白质中的单点突变而与蛋白质中的氨基酸取代有关。TTR基因（ATTRv淀粉样变性）。但是，野生型TTR（TTR wt）具有固有的淀粉样变性潜力，特别是改变生理条件和衰老，导致80岁以上人群的TTR聚集，是非遗传性ATTRwt淀粉样变性的原因。在正常的生理条件下，TTR wt以相同亚基的四聚体形式形成，形成一个中央疏水通道，小分子可以结合，就像天然配体甲状腺素一样（T ₄）。但是，TTR产生淀粉样变性的变体表现出降低的稳定性，并且在特定条件下，解离为部分错误折叠的单体，这些单体聚集并聚合为淀粉样原纤维。因此，这些淀粉样蛋白的治疗策略可能针对疾病过程中的不同步骤，例如降低血浆中的TTR（TTRv）变异，稳定TTR，抑制TTR聚集和聚合或破坏原纤维。虽然旨在降低突变型TTR的策略主要涉及遗传方法，无论是通过肝移植还是采用特定寡核苷酸或沉默RNA的最新技术，但淀粉样蛋白生成级联反应的其他步骤可能会受到药理化合物的损害，即TTR稳定剂，TTR抑制剂聚集和淀粉样蛋白干扰物。