中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (4): 1096-1097.doi: 10.4103/NRR.NRR-D-24-00056

• 观点:退行性病与再生 • 上一篇    下一篇

一种治疗转甲状腺素淀粉样变性药物的设计和重新设计之旅

  

  • 出版日期:2025-04-15 发布日期:2024-07-01

Design and redesign journey of a drug for transthyretin amyloidosis

Francisca Pinheiro, Salvador Ventura*   

  1. Institut de Biotecnologia i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain
  • Online:2025-04-15 Published:2024-07-01
  • Contact: Salvador Ventura, PhD,salvador.ventura@uab.cat.
  • Supported by:
    This work was funded by the Spanish Ministry of Science and Innovation (PDC2021-120914-I00), the Universitat Autònoma de Barcelona (PROOF OF CONCEPT 2020), and ICREA, ICREA-Academia 2015 and 2020 (to SV).

摘要:

Abstract: The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis. Transthyretin (TTR) is one of the > 30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis (ATTR). ATTR comprises senile systemic amyloidosis, which is linked to wildtype (WT) TTR aggregation, and hereditary ATTR, a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants. Senile systemic amyloidosis is a prevalent age-related amyloidosis, affecting up to 25% of the population over 80 years of age, and is characterized by the build-up of TTR fibrils in the myocardium. Regarding hereditary ATTR, the clinical presentation is highly heterogeneous, primarily affecting the peripheral nervous system (familial amyloid polyneuropathy – FAP) or the heart (familial amyloid cardiomyopathy). In rare cases, aggregation develops in the central nervous system, giving rise to a phenotype known as familial leptomeningeal amyloidosis (Carroll et al., 2022).