Ferroptosis as an emerging target in sickle cell disease
Vitor Fortuna, Jaqueline Costa Lima, Gabriel F. Oliveira, Yasmin Souza Caldas de Oliveira, Bruk Getachew, Sergeï Nekhai, Michael Aschner, Yousef Tizabi
Abstract
Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.