β-amyloid protein induces mitophagy-dependent ferroptosis through the CD36/PINK/PARKIN pathway leading to blood–brain barrier destruction in Alzheimer’s disease

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: May 26, 2022

Blood-brain barrier (BBB) dysfunction may occur at the onset of Alzheimer's disease (AD). Pericytes are a vital part neurovascular unit and BBB, acting as gatekeepers BBB. Amyloid β (Aβ) deposition neurofibrillary tangles in brain central pathological features AD. CD36 promotes vascular amyloid leads to damage, dysfunction, cognitive deficits. However, molecular mechanism by which pericytes BBB disrupted remains unclear.To investigate effect low-dose Aβ1-40 administration on pericyte outcome injury.We selected 6-month-old 9-month-old APP/PS1 mice wild-type (WT) same strain, age, sex controls. We assessed using PET/CT. Brain were extracted cocultured with endothelial cells (bEnd.3) generate an vitro model observe Furthermore, we explored intracellular degradation related mechanisms cells.BBB permeability number decreased mice. increased vivo downregulated expression CD36, reversed Aβ-induced changes permeability. was uptaked high expression. observed that this molecule inhibited proliferation, caused mitochondrial mitophagy. Finally, confirmed induced mitophagy-dependent ferroptosis through CD36/PINK1/Parkin pathway.PDGFRβ (a marker pericytes), Aβ colocalized vivo, disruption upregulating pericytes. The destroys involves induction pathway.

Language: Английский

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The emerging roles of MAPK-AMPK in ferroptosis regulatory network

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 14, 2023

Abstract Ferroptosis, a newform of programmed cell death, driven by peroxidative damages polyunsaturated-fatty-acid-containing phospholipids in cellular membranes and is extremely dependent on iron ions, which differs characteristics from traditional death has attracted greater attention. Based the curiosity this new form regulated there tremendous progress field mechanistic understanding ferroptosis recent years. Ferroptosis closely associated with development many diseases involved related signaling pathways. Not only variety oncoproteins tumor suppressors can regulate ferroptosis, but multiple oncogenic pathways also have regulatory effect ferroptosis. results accumulation large amounts lipid peroxides thus involving onset oxidative stress energy responses. The MAPK pathway plays critical role AMPK acts as sensor regulation response. Moreover, activation induce occurrence autophagy-dependent p53-activated In years, been advances study molecular mechanisms to both review, we will summarize MAPK-AMPK regulates Meanwhile, sorted out mysterious relationship between AMPK, described crosstalk among pathways, summarized relevant inducers targeting network. This provide for future research vision cancer treatment strategies.

Language: Английский

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Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102035 - 102035

Published: Aug. 23, 2023

Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), Huntington's (HD), so on. Treating presents opportunities as well challenges for diseases. This review provides a comprehensive overview underlying mechanisms that contribute to occurrence ferroptosis, their implications pathogenesis advancement major disorders. Meanwhile, we summarize interaction between other types diseases contribution corresponding drug development. In addition, specifically recent advances developing therapeutic means targeting these which may guide future approaches effective management devastating medical conditions.

Language: Английский

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The emerging role of ferroptosis in female reproductive disorders

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115415 - 115415

Published: Sept. 4, 2023

Iron, as an essential trace element for the organism, is vital maintaining organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis a novel form of programmed cell death distinguished by overload lipid peroxidation, which unique from autophagy, apoptosis necrosis, more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis associated with development female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), cancer (OC), preeclampsia (PE) spontaneous abortion (SA). Pathways genes may participate in processes regulate granulosa proliferation secretion, oocyte development, reserve function, early embryonic placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates occurrence research progress FRDs, view to providing literature references clinical targeting -related pathways regulatory factors management FRDs.

Language: Английский

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The crosstalk between exosomal miRNA and ferroptosis: A narrative review

Biology of the Cell, Journal Year: 2025, Volume and Issue: 117(1)

Published: Jan. 1, 2025

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive negative regulation it. For example, increased levels reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it not dependent on caspases, but iron. Exosomes are membrane-bound vesicles with size about 30 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, proteins, which genetically similar their cells origin. found in all bodily fluids, blood, saliva, urine. Cells often release exosomes after fusion membrane. They play an important role immune cell-cell communication. miRNAs, noncoding RNAs length 18 24 nucleotides, involved regulating gene expression transcription. Emerging data suggests exosomal miRNAs implicated pathophysiological cells, metastasis, drug resistance, death. In addition, functional studies have indicated can key modulation by Therefore, this review, given importance ferroptosis, we decided elucidate relationship between diseases.

Language: Английский

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