The emerging roles of ferroptosis in cells of the central nervous system

Li, Yuyao; Xiao, Dongqiong; Wang, Xiaodong

doi:10.3389/fnins.2022.1032140

Cited by 14 publications

(3 citation statements)

References 102 publications

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“…Recent studies emphasize the potential link between ferroptosis in white matter damage and PD, particularly focusing on oligodendrocytes ( Wang et al, 2022 ). Dysregulated iron metabolism within oligodendrocytes could lead to iron accumulation, increasing the risk of ferroptosis and thereby harming white matter health ( Ge et al, 2022 ; Li et al, 2022 ). Excessive iron accumulation may induce oxidative stress and trigger ferroptosis, further exacerbating neuronal damage.…”

Section: Crosstalk Between Pd Immune Cells and White Matter Damagementioning

confidence: 99%

The mechanisms of white matter injury and immune system crosstalk in promoting the progression of Parkinson’s disease: a narrative review

Ma,

Geng,

Liu

et al. 2024

Front. Aging Neurosci.

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Parkinson’s disease (PD) is neurodegenerative disease in middle-aged and elderly people with some pathological mechanisms including immune disorder, neuroinflammation, white matter injury and abnormal aggregation of alpha-synuclein, etc. New research suggests that white matter injury may be important in the development of PD, but how inflammation, the immune system, and white matter damage interact to harm dopamine neurons is not yet understood. Therefore, it is particularly important to delve into the crosstalk between immune cells in the central and peripheral nervous system based on the study of white matter damage in PD. This crosstalk could not only exacerbate the pathological process of PD but may also reveal new therapeutic targets. By understanding how immune cells penetrate through the blood–brain barrier and activate inflammatory responses within the central nervous system, we can better grasp the impact of structural destruction of white matter in PD and explore how this process can be modulated to mitigate or combat disease progression. Microglia, astrocytes, oligodendrocytes and peripheral immune cells (especially T cells) play a central role in its pathological process where these immune cells produce and respond to pro-inflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), and white matter injury causes microglia to become pro-inflammatory and release inflammatory mediators, which attract more immune cells to the damaged area, increasing the inflammatory response. Moreover, white matter damage also causes dysfunction of blood–brain barrier, allows peripheral immune cells and inflammatory factors to invade the brain further, and enhances microglia activation forming a vicious circle that intensifies neuroinflammation. And these factors collectively promote the neuroinflammatory environment and neurodegeneration changes of PD. Overall, these findings not only deepen our understanding of the complexity of PD, but also provide new targets for the development of therapeutic strategies focused on inflammation and immune regulation mechanisms. In summary, this review provided the theoretical basis for clarifying the pathogenesis of PD, summarized the association between white matter damage and the immune cells in the central and peripheral nervous systems, and then emphasized their potential specific mechanisms of achieving crosstalk with further aggravating the pathological process of PD.

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Section: Crosstalk Between Pd Immune Cells and White Matter Damagementioning

confidence: 99%

The mechanisms of white matter injury and immune system crosstalk in promoting the progression of Parkinson’s disease: a narrative review

Ma,

Geng,

Liu

et al. 2024

Front. Aging Neurosci.

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“…11 Ferroptosis affects all cell types in the nervous system, including neurons, glial cells, and pericytes. 12 Microglia are the primary iron-accumulating cells in disease. 13,14 Recent evidence indicates that iron-laden microglia have a critical role in ferroptosis associated with neurodegeneration.…”

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confidence: 99%

What Is the Role of Ferroptosis in Neurodegeneration?

Benarroch

2023

Neurology

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Ferroptosis is a unique form of programmed cell death pathway that is mechanistically different from necrosis, apoptosis, or autophagy.1 Ferroptosis is induced by reactive oxygen species (ROS) originating from multiple sources, especially accumulation of free intracellular divalent iron (Fe2+), leading to peroxidation of polyunsaturated fatty acids (PUFAs) and resulting in membrane damage (Figure). One major trigger of ferroptosis is decreased availability of intracellular antioxidant enzymes, particularly glutathione peroxidases (GPXs).1-7 Because of its high lipid concentration and oxygen consumption rate, the nervous tissue is extremely vulnerable to oxidative damage and ferroptosis. With aging, iron accumulates in the brain, which predisposes to and exacerbates these processes.8 Iron promotes ferroptosis both directly and as a cofactor required for the activity of enzymes mediating redox reactions and lipid peroxidation.9,10 Epigenetic regulation can determine cell sensitivity to ferroptosis by affecting intracellular iron levels, oxidative stress, and lipid metabolism.11 Ferroptosis affects all cell types in the nervous system, including neurons, glial cells, and pericytes.12 Microglia are the primary iron-accumulating cells in disease.13,14 Recent evidence indicates that iron-laden microglia have a critical role in ferroptosis associated with neurodegeneration.15 Studies in vitro, in experimental disease models, and in human brain tissue indicate that iron accumulation, oxidative stress, and lipid peroxidation are major disease mechanisms in a wide range of neurologic disorders. These studies also suggest that the different components of the ferroptosis pathway are potential targets for therapeutic intervention. The mechanisms of ferroptosis and its role in neurologic disorders have been the subject of several recent comprehensive reviews.7,8,16-21 Some of these concepts pertinent to neurodegeneration will be emphasized in this study.

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“…Growing evidence indicates that ferroptosis plays key roles in neurological diseases such as stroke, traumatic brain injury (TBI), and neurodegenerative diseases [Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), vascular dementia (VD), Huntington's disease (HD)] (Costa et al, 2023 ; Du et al, 2023 ). Ferroptosis inhibition has been shown to protect neurons and ameliorate cognitive impairment in various disease animal models (Li et al, 2022 ; Zhang et al, 2023 ). However, to date, the underlying mechanisms that how ferroptosis causes neurological injuries are still unclear.…”

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confidence: 99%