BDNF-altering cell death mechanisms of brain disorders: pyroptosis and/or ferroptosis? A systematic review

Abstract

The brain plays a central role in controlling and regulating bodily activities. Given its significance, the brain needs to remain in optimal condition to function properly. Neurodegenerative diseases arise when the mechanisms maintaining brain homeostasis fail, resulting in prolonged and uncontrolled activation of cell death pathways. Increasingly, researchers are focusing on specific types of cell death, such as ferroptosis and pyroptosis, due to their potential as targets for preventing and treating neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a crucial growth factor for neurogenesis, neuronal survival, and maintenance, and is thus implicated in cell death mechanisms. This review aims to elucidate the role of BDNF in the ferroptosis and pyroptosis mechanisms that impact brain health. To achieve this, three databases – PubMed, Scopus, and Web of Science – were searched for relevant studies, yielding 95 articles, of which only 14 were aligned with the study’s aim. Ferroptosis (iron-dependent cell death) and pyroptosis (inflammatory cell death) are distinct modes of cell death; however, this review found both mechanisms are associated with oxidative stress. Consequently, the findings suggest that ferroptosis and pyroptosis collectively impact brain health conditions such as depression, cognitive deficiencies, and anxiety, which are notably linked to reduced BDNF levels.

Keywords

• ferroptosis
• pyroptosis
• cell death
• brain-derived neurotrophic factor
• brain health