Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are a diverse class of diseases attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The pathogenesis of neurodegenerative diseases is complex and diverse, often involving mitochondrial dysfunction, neuroinflammation, and epigenetic changes. However, the pathogenesis of neurodegenerative diseases has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, a newly discovered iron-dependent and lipid peroxidation-driven type of programmed cell death, provides another explanation for the occurrence and progression of neurodegenerative diseases. Here, we provide an overview of the process and regulation mechanisms of ferroptosis, and summarize current research progresses that support the contribution of ferroptosis to the pathogenesis of neurodegenerative diseases. A comprehensive understanding of the emerging roles of ferroptosis in neurodegenerative diseases will shed light on the development of novel therapeutic technologies and strategies for slowing down the progression of these diseases.

Identification of Key Ferroptosis-Related Genes in the Peripheral Blood of Patients with Relapsing-Remitting Multiple Sclerosis and Its Diagnostic Value

“…Iron dysregulation is a significant factor in the development of MS, and ferroptosis-related signaling pathways have emerged as potential diagnostic biomarkers and therapeutic targets for various neurodegenerative diseases [ 25 ]. However, the exact role and specific molecular mechanism of ferroptosis in MS remain unclear and require further exploration.…”

Machine learning models identify ferroptosis-related genes as potential diagnostic biomarkers for Alzheimer’s disease

“…Several studies have used gene expression datasets downloaded from databases to clarify the biological mechanisms underlying AD development for disease prediction ( Bellenguez et al, 2022 ; Wang et al, 2022b ). On the basis of some research, ferroptosis has been shown to be involved in the pathological process of AD ( Ayton et al, 2020 ; Sun Y. et al, 2022 ; Wang et al, 2022c ). In the previous studies, to promote the development of diagnosis, researchers have explored candidate factors such as immune-based biomarkers ( He et al, 2022 ), DNA methylation-related biomarkers ( Chen et al, 2022 ) and aging-related biomarkers ( Zhang Q. et al, 2022 ).…”

Erythrocytes as Messengers for Information and Energy Exchange between Cells

“…Ferroptosis is characterized by iron overload, peroxidation of lipids and low activity of the selenium-containing enzyme glutathione peroxidase 4. Ferroptosis has been associated with several pathological conditions including neurological diseases such as Alzheimer's disease [85]. Transcriptomic analysis reveals changed expression levels of many ferroptosis-related genes in Alzheimer's disease patients [86], including the selenium-containing enzyme glutathione peroxidase 4.…”