Iron and Ferroptosis as Therapeutic Targets in Alzheimer's Disease

Neurotherapeutics, Journal Year: 2020, Volume and Issue: 18(1), P. 252 - 264

Published: Oct. 27, 2020

Language: Английский

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α‐Lipoic acid alleviates ferroptosis in the MPP⁺‐induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway

Cell Biology International, Journal Year: 2020, Volume and Issue: 45(2), P. 422 - 431

Published: Nov. 26, 2020

Abstract Parkinson's disease (PD) is a typical neurodegenerative disease. α‐Lipoic acid (α‐LA) can reduce the incidence of neuropathy. The present study explored role and mechanism α‐LA in 1‐methyl‐4‐phenylpyridinium (MPP + )‐induced cell model PD. PD was induced via treating PC12 cells with MPP at different concentrations. effects on were assessed from viability ferroptosis. Cell detected using counting kit‐8 assay. Malondialdehyde (MDA), 4‐hydroxynonenal (4‐HNE), iron, reactive xygen species (ROS), glutathione (GSH) concentrations, ferroptosis‐related protein SLC7A11 GPx4 expressions used for ferroptosis evaluation. p‐PI3K, p‐Akt, nuclear factor erythroid 2‐related 2 (Nrf2) levels detected. PI3K/Akt/Nrf2 pathway inhibitors applied to verify protection against ‐induced decreased ‐reduced as presented by increased MDA, 4‐HNE, ROS reduced GSH marker proteins (SLC7A11 GPx4). attenuated decline activated after treatment. Inhibiting weakened We highlighted that alleviated decrease activating pathway.

Language: Английский

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A Review on Lactoferrin and Central Nervous System Diseases

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1810 - 1810

Published: July 17, 2021

Central nervous system (CNS) diseases are currently one of the major health issues around world. Most CNS disorders characterized by high oxidative stress levels and intense inflammatory responses in affected tissues. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein, plays significant role anti-inflammatory, antibacterial, antiviral, reactive oxygen species (ROS) modulator, antitumor immunity, anti-apoptotic processes. Previous studies have shown that Lf is abnormally expressed variety neurological diseases, especially neurodegenerative diseases. Recently, promotion neurodevelopment neuroprotection has attracted widespread attention, could be exploited both as an active therapeutic agent drug nanocarrier. However, our understanding roles proteins initiation or progression limited, regulating neurogenesis. This review highlights recent advances pharmacological effects including cerebrovascular disease, developmental delays children, brain tumors.

Language: Английский

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Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles

Journal of Nanobiotechnology, Journal Year: 2021, Volume and Issue: 19(1)

Published: Oct. 18, 2021

Iron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) proven due its antioxidant anti-inflammatory properties. poor solubility low bioavailability QC also led researchers make various QC-involved overcome these limitations. We wondered how high doses or prolonged treatment with conjugated superparamagnetic (QCSPIONs) could improve cognitive dysfunction promote neurogenesis without any toxicity. It can be explained that inhibits aggregation acts against overload iron-chelating activity, homeostasis genes regulation, radical scavenging, attenuation Fenton/Haber-Weiss reaction. In this review, first, we present brain homeostasis, molecular mechanisms induced neurotoxicity, role dementia-associated diseases. Then by providing evidence discuss neutralizes finally, a brief comparison between conventional chelators. highlight supplementation especially form reduces neurotoxicity clinical application.

Language: Английский

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Elucidating the Interaction of Human Ferritin with Quercetin and Naringenin: Implication of Natural Products in Neurodegenerative Diseases: Molecular Docking and Dynamics Simulation Insight

ACS Omega, Journal Year: 2021, Volume and Issue: 6(11), P. 7922 - 7930

Published: March 11, 2021

Recent research has advocated the significant contribution of metal dyshomeostasis in developing and progressing Alzheimer's disease (AD). Disruption homeostasis creates an imbalance ions that causes neuronal dysfunction death. Flavonoids such as quercetin naringenin play essential role iron are widely explored treating various complex diseases. Iron is a critical player many physiological activities, hence, its for normal functioning brain. deficiency overload contribute to AD development, highlighting importance maintaining homeostasis. Ferritin protein associated with storage sequestration excess ferrous iron, playing pivotal levels. most common polyphenolic compounds present human diet known exert multiple neuroprotective actions. Naringenin extensively polyphenols having broad range therapeutic potential ranging from cancers neurodegenerative disorders. This study aims investigate their binding, employing molecular docking dynamics (MD) simulation light these polyphenols' ferritin's AD. In this study, we performed structure-based ferritin. First, binding affinity toward ferritin was estimated, then close interactions were find stable poses. All-atom 100 ns MD simulations further escorted followed by principal component free energy landscape analyses. The dynamic studies helped conformational dynamic, structural stability, interaction mechanism naringenin. analysis suggested stabilizes throughout period leads fewer deviations. gives insight at atomistic level into between ferritin, thereby aiding understanding activity drug binding. clinically participates occurrence

Language: Английский

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