Autophagy mediates an amplification loop during ferroptosis

Cell Death and Disease, Год журнала: 2023, Номер 14(7)

Опубликована: Июль 25, 2023

Ferroptosis, a programmed cell death, has been identified and associated with cancer various other diseases. Ferroptosis is defined as reactive oxygen species (ROS)-dependent death related to iron accumulation lipid peroxidation, which different from apoptosis, necrosis, autophagy, forms of death. However, accumulating evidence revealed link between autophagy ferroptosis at the molecular level suggested that involved in regulating iron-dependent peroxidation ROS during ferroptosis. Understanding roles pathophysiological processes may provide effective strategies for treatment ferroptosis-related In this review, we summarize current knowledge regarding regulatory mechanisms underlying ferroptosis, including metabolism, its association pathway. addition, discuss contribution elucidate role enhancer ROS-dependent

Язык: Английский

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Oxidative Stress in Age-Related Neurodegenerative Diseases: An Overview of Recent Tools and Findings

Antioxidants, Год журнала: 2023, Номер 12(1), С. 131 - 131

Опубликована: Янв. 5, 2023

Reactive oxygen species (ROS) have been described to induce a broad range of redox-dependent signaling reactions in physiological conditions. Nevertheless, an excessive accumulation ROS leads oxidative stress, which was traditionally considered as detrimental for cells and organisms, due the damage they cause biomolecules. During ageing, elevated levels result damaged proteins, may exhibit altered enzymatic function or physical properties (e.g., aggregation propensity). Emerging evidence also highlights relationship between stress age-related pathologies, such protein misfolding-based neurodegenerative diseases Parkinson’s (PD), Alzheimer’s (AD) Huntington’s (HD) diseases). In this review we aim introduce role physiology pathology then focus on state-of-the-art techniques available detect quantify oxidized proteins live vivo, providing guide those aiming characterize ageing diseases. Lastly, discuss recently published data neurological disorders.

Язык: Английский

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Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer’s Disease: Role of Glutathione and Metal Ions

ACS Chemical Neuroscience, Год журнала: 2023, Номер 14(17), С. 2944 - 2954

Опубликована: Авг. 10, 2023

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder that affects millions of people worldwide. Although the pathogenesis remains obscure, there are two dominant causal hypotheses. Since last three decades, amyloid beta (Aβ) deposition was most prominent hypothesis, other tau hyperphosphorylation hypothesis. The confirmed diagnostic criterion for AD presence neurofibrillary tangles (NFTs) composed hyperphosphorylated toxic oligomeric Aβ in autopsied brain. Consistent with these hypotheses, oxidative stress (OS) garnering major attention research. OS results from imbalance pro-oxidants antioxidants. There a considerable debate scientific community on which process occurs first, or plaque deposition/tau hyperphosphorylation. Based recent observations various laboratories including ours along critical analysis those information, we believe early event leads to as well dimerization protein its subsequent This hypothesis immediately suggests consideration novel therapeutic approaches include antioxidants involving glutathione enrichment brain by supplementation without iron chelator.

Язык: Английский

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Micro- and Nanosized Carriers for Nose-to-Brain Drug Delivery in Neurodegenerative Disorders

Biomedicines, Год журнала: 2022, Номер 10(7), С. 1706 - 1706

Опубликована: Июль 14, 2022

Neurodegenerative disorders (NDs) have become a serious health problem worldwide due to the rapid increase in number of people that are affected and constantly aging population. Among all NDs, Alzheimer’s Parkinson’s disease most common, many efforts been made development effective reliable therapeutic strategies. The intranasal route drug administration offers numerous advantages, such as bypassing blood–brain barrier providing direct entrance brain through olfactory trigeminal neurons. present review summarizes available information on recent advances micro- nanoscale nose-to-brain drug-delivery systems novel strategy for treatment disease. Specifically, polymer- lipid-base nanoparticles studied feasible approach bioavailability certain drugs. Furthermore, nanocomposites discussed suitable formulation into nasal cavity.

Язык: Английский

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Brain Iron Metabolism, Redox Balance and Neurological Diseases

Antioxidants, Год журнала: 2023, Номер 12(6), С. 1289 - 1289

Опубликована: Июнь 16, 2023

The incidence of neurological diseases, such as Parkinson’s disease, Alzheimer’s disease and stroke, is increasing. An increasing number studies have correlated these diseases with brain iron overload the resulting oxidative damage. Brain deficiency has also been closely linked to neurodevelopment. These disorders seriously affect physical mental health patients bring heavy economic burdens families society. Therefore, it important maintain homeostasis understand mechanism affecting reactive oxygen species (ROS) balance, in neural damage, cell death and, ultimately, leading development disease. Evidence shown that many therapies targeting ROS imbalances good preventive therapeutic effects on diseases. This review highlights molecular mechanisms, pathogenesis treatment strategies metabolism

Язык: Английский

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Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Ноя. 18, 2023

Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, prospectively associated with pigment epithelial (RPE) senescence. However, mechanism RPE cell remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells D-galactose-treated C57 mice were used examine cause elevated iron in Ferric ammonium citrate (FAC)-treated elucidated overload-induced Molecular biology techniques for assessment metabolism, cellular senescence, autophagy, mitochondrial function vivo vitro. We found that level was increased during process. Ferritin, major storage protein, negatively correlated intracellular levels NCOA4, cargo receptor ferritinophagy, mediates degradation ferritin contributes accumulation. Besides, we overload leads dysfunction. As result, DNA (mtDNA) released from damaged mitochondria cytoplasm. Cytoplasm mtDNA activates cGAS-STING pathway promotes inflammatory senescence-associated secretory phenotype (SASP) Meanwhile, chelator Deferoxamine (DFO) significantly rescues retinopathy induced by FAC or D-gal mice. Taken together, these findings imply derived NCOA4-mediated ferritinophagy causes via pathway. Inhibiting accumulation may represent promising therapeutic approach diseases such as AMD.

Язык: Английский

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The function of sphingolipids in different pathogenesis of Alzheimer's disease: A comprehensive review

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116071 - 116071

Опубликована: Янв. 6, 2024

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is importance in understanding the neuropathological progression Alzheimer's disease (AD). AD characterized by accumulation extracellular deposits amyloid β-peptide (Aβ) intraneuronal aggregates microtubule-associated protein tau. Critical roles Aβ oligomer deposited ganglioside GM1 could be formed as "seed" from insoluble GAβ polymer initiating pathogenic process, while tau might also mediate SPLs their toxicity. interaction between ceramide α-Synuclein (α-Syn) accelerates aggregation ferroptosis exacerbates pathogenesis AD. For instance, reducing levels can mitigate α-Syn inhibit progression. Meanwhile, loss may expression APOE4 confer protection against AD, disrupts homeostasis. Moreover, heightened activation sphingomyelinase promotes signaling pathway, leading to exacerbated symptoms. Ferroptosis plays vital role pathological influencing Aβ, tau, APOE, α-Syn. Conversely, development manifestation SPLs. We are compiling emerging techniques (Derivatization IM-MS) sphingolipidomics, overcome challenges diagnosis treatment. In this review, we examined intricate neuro-mechanistic interactions α-Syn, ferroptosis, mediating onset Furthermore, our findings highlight potential targeting underexplored avenue for devising innovative therapeutic strategies

Язык: Английский

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Mitochondrial Transportation, Transplantation, and Subsequent Immune Response in Alzheimer’s Disease: An Update

Molecular Neurobiology, Год журнала: 2024, Номер 61(9), С. 7151 - 7167

Опубликована: Фев. 17, 2024

Язык: Английский

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Inhibition of VDAC1 Rescues Aβ1-42-Induced Mitochondrial Dysfunction and Ferroptosis via Activation of AMPK and Wnt/β-Catenin Pathways

Mediators of Inflammation, Год журнала: 2023, Номер 2023, С. 1 - 13

Опубликована: Фев. 10, 2023

Beta-amyloid (Aβ) accumulation in the brains of Alzheimer's disease (AD) patients leads to mitochondrial dysfunction and ferroptosis neurons. Voltage-dependent anion channel 1 (VDAC1) is a major protein outer membrane. It has been reported that VDAC1 associated with ferroptosis. However, mechanism by which regulates neurons AD remains unclear. This study aimed at investigating action model. In this study, we determined cell viability after treatment Aβ1-42 via MTT assay. The SOD, MDA, ROS, MMP production was measured SOD kit, MDA DCFDA staining, JC-1 staining. memory abilities mice were detected Morris water maze test. expression AMPK/mTOR, Wnt/β-catenin, GPX4 regulated western blotting. Our present showed PC12 cells had decreased viability, increased LDH release, treatment. Meanwhile, induced downregulation ROS generation cells. addition, brain tissue Aβ1-42-treated Further investigation role regulating found all effects reversed inhibition VDAC1. Additionally, activates AMPK/mTOR Wnt/β-catenin pathways. Taken together, these findings demonstrate alleviates activating Wnt/β-catenin.

Язык: Английский

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Complex II ambiguities—FADH2 in the electron transfer system

Journal of Biological Chemistry, Год журнала: 2023, Номер 300(1), С. 105470 - 105470

Опубликована: Ноя. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Язык: Английский

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