This Italian paper tells us about the possibilities of our ATH434, not only in neurodegeneration but also in many other problems. Of course, they do not say a world of 434, but we ATH investors need to understand the possibilities of our drug. Some 15 y ago, it was already demonstrated that mice treated with 434 and PBT2 lived some 20% longer than the controls ( presented in a conference as an abstract ).

Review

J Nutr Biochem

. 2025 Jun:140:109888.

doi: 10.1016/j.jnutbio.2025.109888. Epub 2025 Mar 6.

Iron metabolism and ferroptosis in health and diseases: The crucial role of mitochondria in metabolically active tissues

Angela Catapano ¹, Fabiano Cimmino ², Lidia Petrella ¹, Amelia Pizzella ¹, Margherita D'Angelo ³, Katia Ambrosio ¹, Francesca Marino ⁴, Annarita Sabbatini ⁵, Massimiliano Petrelli ⁶, Barbara Paolini ⁷, Lucio Lucchin ⁸, Gina Cavaliere ⁹, Luigia Cristino ¹⁰, Marianna Crispino ¹¹, Giovanna Trinchese ¹, Maria Pina Mollica ¹

Affiliations Expand

• PMID: 40057002

DOI: 10.1016/j.jnutbio.2025.109888Free article

Abstract

Iron is essential in various physiological processes, but its accumulation leads to oxidative stress and cell damage, thus iron homeostasis has to be tightly regulated. Ferroptosis is an iron-dependent non-apoptotic regulated cell death characterized by iron overload and reactive oxygen species accumulation. Mitochondria are organelles playing a crucial role in iron metabolism and involved in ferroptosis. MitoNEET, a protein of mitochondrial outer membrane, is a key element in this process. Ferroptosis, altering iron levels in several metabolically active organs, is linked to several non-communicable diseases. For example, iron overload in the liver leads to hepatic fibrosis and cirrhosis, accelerating non-alcholic fatty liver diseases progression, in the muscle cells contributes to oxidative damage leading to sarcopenia, and in the brain is associated to neurodegeneration. The aim of this review is to investigate the intricate balance of iron regulation focusing on the role of mitochondria and oxidative stress, and analyzing the ferroptosis implications in health and disease.

Keywords: Ferroptosis; Iron; MitoNEET; Mitochondria; Obesity.


Full paper: https://www.sciencedirect.com/science/article/pii/S0955286325000518?via%3Dihub