Mechanism of Ferroptosis and Its Role in Spinal Cord Injury

Abstract

Ferroptosis is a non-necrotic form of regulated cell death (RCD) that is primarily characterized by iron-dependent membrane lipid peroxidation and is regulated by cysteine transport, glutathione synthesis, and glutathione peroxidase 4 function as well as other proteins including ferroptosis suppressor protein 1. It has been found that ferroptosis played an important role in many diseases, such as neurodegenerative diseases and ischemia-reperfusion injury. Spinal cord injury (SCI), especially traumatic SCI, is an urgent problem worldwide due to its high morbidity and mortality, as well as the destruction of functions of the human body. Various RCDs, including ferroptosis, are found in SCI. Different from necrosis, since RCD is a form of cell death regulated by various molecular mechanisms in cells, the study of the role played by RCD in SCI will contribute to a deeper understanding of the pathophysiological process, as well as the treatment and functional recovery. The present review mainly introduces the main mechanism of ferroptosis and its role in SCI, so as to provide a new idea for further exploration.

Piperine attenuates the inflammation, oxidative stress, and pyroptosis to facilitate recovery from spinal cord injury via autophagy enhancement

“…The primary injury commonly refers to acute SCI resulting from mechanical damage to the spinal cord; this leads to the immediate death of neurons and cannot be treated clinically (Stahel, VanderHeiden, & Finn, 2012). Secondary injury refers to secondary neuronal death caused by ischemia–reperfusion injury, hypoxia, inflammation, oxidative stress, intracellular calcium ion overload, and autophagy impairment, together with various forms of cell death in the lesion area after the primary injury (Li et al, 2022). Methylprednisolone sodium succinate is one of the most commonly used drugs for the prevention of secondary damage; this acts by stabilization of cell membranes and reducing inflammation, but has unavoidable side effects that limit its efficacy (“A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal‐cord injury,” 1990).…”

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

“…In secondary SCI, ferroptosis, characterized by severe lipid peroxidation and disrupted iron metabolism, plays a significant role. Studies using ferroptosis inhibitors and interventions targeting related pathways show promise in reducing ferroptosis, promoting motor recovery, and enhancing neurological function after SCI ( Li et al, 2022b ). Exosomes derived from MSCs, containing ncRNAs like lncGm36569, offer a promising treatment avenue for acute spinal cord injury (ASCI) by targeting ferroptosis.…”

Ferroptosis open a new door for colorectal cancer treatment

“…Other factors affecting ferroptosis include coenzyme Q10 (CoQ10), NADPH, p53, nuclear factor E2 related factor 2 (NRF2), etc. Ferroptosis suppressor protein 1 (FSP1) is localized to the plasma membrane and acts as an NADPH dependent oxidoreductase that reduces ubiquinone CoQ10 to ubiquinol (CoQH2) to prevent lipid oxidation and inhibits ferroptosis ( 80 , 81 ). p53 can inhibit cystine uptake and ferroptosis by down-regulating the expression of SLC7A11 ( 82 ).…”