Drug discovery and amyotrophic lateral sclerosis: Emerging challenges and therapeutic opportunities

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2023

Autores

Soares, P (Autor) Outra; Catia Teixeira (Autor) FCUP; Chavarria, D (Autor) Outra; Silva, FSG (Autor) Outra; Oliveira, PJ (Autor) Outra; Fernanda Borges (Autor) FCUP

Revista

Título: Ageing Research Reviews

Vol. 83

ISSN: 1568-1637

Editora: Elsevier

Indexação

ISI Web of Knowledge - 6 Citações

Outras Informações

ID Authenticus: P-00X-G0Q

DOI: 10.1016/j.arr.2022.101790

Abstract (EN): Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons (MNs) leading to paralysis and, ultimately, death by respiratory failure 3-5 years after diagnosis. Edaravone and Riluzole, the only drugs currently approved for ALS treatment, only provide mild symptomatic relief to patients. Extraordinary progress in understanding the biology of ALS provided new grounds for drug discovery. Over the last two decades, mitochondria and oxidative stress (OS), iron metabolism and ferroptosis, and the major reg-ulators of hypoxia and inflammation - HIF and NF-kappa B - emerged as promising targets for ALS therapeutic intervention. In this review, we focused our attention on these targets to outline and discuss current advances in ALS drug development. Based on the challenges and the roadblocks, we believe that the rational design of multi -target ligands able to modulate the complex network of events behind the disease can provide effective therapies in a foreseeable future.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 20