Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration

Free Radical Biology and Medicine, Journal Year: 2018, Volume and Issue: 133, P. 221 - 233

Published: Sept. 25, 2018

Language: Английский

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Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration

Frontiers in Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: July 10, 2018

Ferroptosis is a newly described form of regulated cell death, distinct from apoptosis, necroptosis and other forms death. induced by disruption glutathione synthesis or inhibition peroxidase 4, exacerbated iron, prevented radical scavengers such as ferrostatin-1, liproxstatin-1 endogenous vitamin E. terminates with mitochondrial dysfunction toxic lipid peroxidation. Although conclusive identification ferroptosis in vivo challenging, several salient very well established features neurodegenerative diseases are consistent ferroptosis, including peroxidation, iron dysregulation. Accordingly, interest the role neurodegeneration escalating specific evidence rapidly emerging. One aspect that has thus far received little attention antioxidant transcription factor nuclear erythroid 2-related 2 (Nrf2). This regulates hundreds genes, which many either directly indirectly involved modulating metabolism glutathione, lipids, function. potentially positions Nrf2 key deterministic component onset outcomes ferroptotic stress. The minimal direct currently available this indicates may be critical for protection against ferroptosis. In contrast, abundant demonstrates enhancing signaling potently neuroprotective models neurodegeneration, although exact mechanism achieved unclear. Further studies required to determine extent effects activation involve prevention

Language: Английский

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Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease

Progress in Neurobiology, Journal Year: 2020, Volume and Issue: 196, P. 101890 - 101890

Published: July 26, 2020

Language: Английский

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Current understanding of metal ions in the pathogenesis of Alzheimer’s disease

Translational Neurodegeneration, Journal Year: 2020, Volume and Issue: 9(1)

Published: April 3, 2020

The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance these ions closely related to onset progression Alzheimer's disease (AD), most common neurodegenerative disorder elderly.Erroneous deposition/distribution different regions induces oxidative stress. stress together or independently promote amyloid-β (Aβ) overproduction by activating β- γ-secretases inhibiting α-secretase, it also causes tau hyperphosphorylation protein kinases, glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase-5 (CDK5), mitogen-activated kinases (MAPKs), etc., phosphatase 2A (PP2A). imbalances can directly indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial autophagic dysfunctions, which cause aggravate Aβ aggregation/accumulation, impair synaptic Even worse, imbalance-induced alterations reversely exacerbate misdistribution deposition. vicious cycles between Aβ/tau abnormalities will eventually lead a chronic neurodegeneration cognitive deficits, seen AD patients.The pathologies affecting multiple cellular/subcellular pathways, disrupted transportation/deposition. Therefore, adjusting balance supplementing chelating may be potential ameliorating pathologies, provides new research directions treatment.

Language: Английский

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Breakdown of an Ironclad Defense System: The Critical Role of NRF2 in Mediating Ferroptosis

Cell chemical biology, Journal Year: 2020, Volume and Issue: 27(4), P. 436 - 447

Published: April 1, 2020

Ferroptosis is a non-apoptotic mode of regulated cell death that iron and lipid peroxidation dependent. As new mechanistic insight into ferroptotic effectors how they are in different disease contexts uncovered, our understanding the physiological pathological relevance this continues to grow. Along these lines, host pharmacological modulators pathway have been identified, targeting proteins involved homeostasis; generation reduction peroxides; or cystine import glutathione metabolism. Also, note, many components ferroptosis cascade target genes transcription factor nuclear erythroid 2-related 2 (NRF2), indicating its critical role mediating response. In review, we discuss vitro, vivo, clinical evidence disease, including brief discussion upstream mediators cascade, NRF2, treat ferroptosis-driven diseases.

Language: Английский

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Iron mediated toxicity and programmed cell death: A review and a re-examination of existing paradigms

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2016, Volume and Issue: 1864(2), P. 399 - 430

Published: Dec. 6, 2016

Language: Английский

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Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care

Journal of Magnetic Resonance Imaging, Journal Year: 2017, Volume and Issue: 46(4), P. 951 - 971

Published: March 10, 2017

Quantitative susceptibility mapping (QSM) has enabled magnetic resonance imaging (MRI) of tissue to advance from simple qualitative detection hypointense blooming artifacts precise quantitative measurement spatial biodistributions. QSM technology may be regarded sufficiently developed and validated warrant wide dissemination for clinical applications isotropic susceptibility, which is dominated by metals in tissue, including iron calcium. These biometals are highly regulated as vital participants normal cellular biochemistry, their dysregulations manifested a variety pathologic processes. Therefore, can used assess important functions disease. To facilitate translation, this review aims organize pertinent information implementing robust automated technique routine MRI practice summarize available knowledge on diseases improve patient care. In brief, generated with postprocessing whenever gradient echo performed. useful that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations paramagnetic iron, bone mineralization, or calcification; all disorders diagnosis surveillance requires contrast agent injection. Clinicians consider integrating into practices sequences relevant protocols. Level Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:951–971.

Language: Английский

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Iron and Alzheimer’s Disease: From Pathogenesis to Therapeutic Implications

Frontiers in Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Sept. 10, 2018

As people age, iron deposits in different areas of the brain may impair normal cognitive function and behavior. Abnormal metabolism generates hydroxyl radicals through Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein DNA structure function, ultimately leads to death. There is an imbalance homeostasis Alzheimer's disease (AD). Excessive contributes deposition β-amyloid formation neurofibrillary tangles, which turn, promotes development AD. Therefore, iron-targeted therapeutic strategies have become a new direction. Iron chelators, such as desferoxamine, deferiprone, deferasirox, clioquinol, received great deal attention obtained good results scientific experiments some clinical trials. Given limitations side effects long-term application traditional alpha-lipoic acid lactoferrin, self-synthesized naturally small molecules, shown very intriguing biological activities blocking Aβ-aggregation, tauopathy neuronal damage. Despite lack evidence for any benefits, conjecture that chelation, with special focus on ions, valuable approach treating AD remains widespread.

Language: Английский

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Iron and dopamine: a toxic couple

Brain, Journal Year: 2016, Volume and Issue: 139(4), P. 1026 - 1035

Published: March 8, 2016

Iron accumulation is a cardinal feature of degenerating regions in the Parkinson's disease brain. As potent pro-oxidant, redox-active iron may be key player upstream mechanisms that precipitate cell death this disorder. Although an elevation brain levels normal ageing, increase greater disease; on other hand, effects are most marked nigrostriatal dopaminergic system. In Update, we explain neurodegeneration affected result from redox couple formed by and dopamine itself, discuss clinical implications molecular trait dynamic rapidly moving area research. has long been associated with disease. Double Hare describe how form toxic creates hazardous chemical environment inside cells. This process represent both mechanism disease, viable target for new therapies.

Language: Английский

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Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 17(11), P. 804 - 822

Published: Sept. 28, 2018

Language: Английский

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