Interaction between macrophages and ferroptosis

Cell Death and Disease, Год журнала: 2022, Номер 13(4)

Опубликована: Апрель 16, 2022

Abstract Ferroptosis, a newly discovered iron-dependent cell death pathway, is characterized by lipid peroxidation and GSH depletion mediated iron metabolism morphologically, biologically genetically different from other programmed deaths. Besides, ferroptosis usually found accompanied inflammatory reactions. So far, it has been participating in the development of many kinds diseases. Macrophages are group immune cells that widely exist our body for host defense play an important role tissue homeostasis mediating inflammation regulating iron, amino acid metabolisms through their unique functions like phagocytosis efferocytosis, cytokines secretion ROS production under polarization. According to these common points characteristics macrophages functions, it’s obvious there must be relationship between ferroptosis. Therefore, review aims at revealing interaction concerning three integrating application certain curing diseases, mostly cancer. Finally, we also provide inspirations further studies therapy some diseases targeting resident distinct tissues regulate Facts Ferroptosis considered as form its nonapoptotic hydroperoxide, metabolisms. playing crucial part various including hepatic neurological cancer, etc. phagocytic cells, existing owning such production. proved participate initiating reactions maintain balance body. Recent try treat cancer altering macrophages’ polarization which damages tumor microenvironment induces cells. Open questions How do specifically? Can use treating than cancer? What can related macrophages? Is more effective therapies when diseases?

Язык: Английский

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Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(8), С. 4176 - 4176

Опубликована: Апрель 10, 2022

Parkinson’s disease (PD) is an aging-related and the second most common neurodegenerative after Alzheimer’s disease. The main symptoms of PD are movement disorders accompanied with deficiency neurotransmitter dopamine (DA) in striatum due to cell death nigrostriatal DA neurons. Two histopathological hallmarks exist PD: cytosolic inclusion bodies termed Lewy that mainly consist α-synuclein protein, oligomers which produced by misfolding regarded be neurotoxic, causing death; black pigments neuromelanin (NM) contained neurons markedly decrease PD. synthesis human NM similar melanin melanocytes; skin via DOPAquinone (DQ) tyrosinase, whereas DAquinone (DAQ) tyrosine hydroxylase (TH) aromatic L-amino acid decarboxylase (AADC). cytoplasm highly reactive assumed oxidized spontaneously or unidentified tyrosinase DAQ then, synthesized NM. Intracellular accumulation above a specific threshold has been reported associated neuron phenotypes. This review reports recent progress biosynthesis pathophysiology

Язык: Английский

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Cerebral Iron Deposition in Neurodegeneration

Biomolecules, Год журнала: 2022, Номер 12(5), С. 714 - 714

Опубликована: Май 17, 2022

Disruption of cerebral iron regulation appears to have a role in aging and the pathogenesis various neurodegenerative disorders. Possible unfavorable impacts accumulation include reactive oxygen species generation, induction ferroptosis, acceleration inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow examination macroscopic patterns brain deposits vivo, while modern analytical methods ex vivo enable determination metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes whole brain, cellular, subcellular diseases genetic sporadic origin. We provide an update on mechanisms, biomarkers, effects these disorders, focusing recent publications. In Parkinson’s disease, Friedreich’s several disorders neurodegeneration with group, there is focal siderosis, typically regions most pronounced neuropathological second group including multiple sclerosis, Alzheimer’s amyotrophic lateral sclerosis shows globus pallidus, caudate, putamen, cortical regions. Yet, other such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest diffuse deep gray matter pattern comparable even more extensive than that observed during normal aging. On microscopic level, are mostly dystrophic microglia variably accompanied by iron-laden macrophages astrocytes, implicating changes blood–brain barrier disturbance accumulation. Options potential benefits reducing strategies discussed. Future research investigating whether predispositions play Fe necessary. If confirmed, prevention further uptake individuals at risk may be key for preventing

Язык: Английский

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Iron Metabolism in Aging and Age-Related Diseases

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3612 - 3612

Опубликована: Март 25, 2022

Iron is a trace metal element necessary to maintain life and also involved in variety of biological processes. Aging refers the natural process which physiological functions various systems, organs, tissues decline, affected by genetic environmental factors. Therefore, it imperative investigate relationship between iron metabolism aging-related diseases, including neurodegenerative diseases. During aging, accumulation nonheme destroys stability intracellular environment. The destruction homeostasis can induce cell damage producing hydroxyl free radicals, leading mitochondrial dysfunction, brain even organismal aging. In this review, we have briefly summarized role metabolic body, then discussed recent developments aging age-related finally, explored some chelators as treatment strategies for those disorders. Understanding roles diseases will fill knowledge gap field. This review could provide new insights into research on

Язык: Английский

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The heterogeneity of Parkinson’s disease

Journal of Neural Transmission, Год журнала: 2023, Номер 130(6), С. 827 - 838

Опубликована: Май 11, 2023

The heterogeneity of Parkinson's disease (PD), i.e. the various clinical phenotypes, pathological findings, genetic predispositions and probably also implicated pathophysiological pathways pose a major challenge for future research projects therapeutic trail design. We outline several concepts, mechanisms, including presumed roles α-synuclein misfolding aggregation, Lewy bodies, oxidative stress, iron melanin, deficient autophagy processes, insulin incretin signaling, T-cell autoimmunity, gut-brain axis evidence that microbial (viral) agents may induce molecular hallmarks neurodegeneration. hypothesis is discussed, whether PD might indeed be triggered by exogenous (infectious) in susceptible individuals upon entry via olfactory bulb (brain first) or gut (body-first), which would support idea mechanisms change over time. unresolved have contributed to failure past trials, attempted slow course PD. thus conclude patients need personalized approaches tailored specific phenomenological etiologic subtypes disease.

Язык: Английский

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Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Июнь 28, 2022

Neurodegenerative diseases are a diverse class of attributed to chronic progressive neuronal degeneration and synaptic loss in the brain and/or spinal cord, including Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis multiple sclerosis. The pathogenesis neurodegenerative is complex diverse, often involving mitochondrial dysfunction, neuroinflammation, epigenetic changes. However, has not been fully elucidated. Recently, accumulating evidence revealed that ferroptosis, newly discovered iron-dependent lipid peroxidation-driven type programmed cell death, provides another explanation for occurrence progression diseases. Here, we provide an overview process regulation mechanisms summarize current research progresses support contribution ferroptosis A comprehensive understanding emerging roles will shed light on development novel therapeutic technologies strategies slowing down these

Язык: Английский

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The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease

Journal of Neural Transmission, Год журнала: 2023, Номер 130(5), С. 611 - 625

Опубликована: Март 20, 2023

Abstract The dark pigment neuromelanin (NM) is abundant in cell bodies of dopamine (DA) neurons the substantia nigra (SN) and norepinephrine (NE) locus coeruleus (LC) human brain. During progression Parkinson’s disease (PD), together with degeneration respective catecholamine (CA) neurons, NM levels SN LC markedly decrease. However, questions remain among others on how associated PD it synthesized. biosynthesis pathway brain has been controversial because presence tyrosinase CA elusive. We propose following synthesis these neurons: (1) Tyrosine converted by tyrosine hydroxylase (TH) to L-3,4-dihydroxyphenylalanine (L-DOPA), which aromatic L-amino acid decarboxylase DA, β-hydroxylase NE; (2) DA or NE autoxidized quinone (DAQ) (NEQ); (3) DAQ NEQ eumelanic (euNM) pheomelanic (pheoNM) absence cysteine, respectively. This process involves proteins as cysteine source iron. also discuss whether amounts per neuromelanin-positive (NM + ) neuron are higher brain, quantitatively correlates neurodegeneration, an active lifestyle may reduce formation.

Язык: Английский

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Lewy bodies, iron, inflammation and neuromelanin: pathological aspects underlying Parkinson’s disease

Journal of Neural Transmission, Год журнала: 2023, Номер 130(5), С. 627 - 646

Опубликована: Апрель 16, 2023

Abstract Since the description of some peculiar symptoms by James Parkinson in 1817, attempts have been made to define its cause or at least enlighten pathology “Parkinson’s disease (PD).” The vast majority PD subtypes and most cases sporadic share Lewy bodies (LBs) as a characteristic pathological hallmark. However, processes underlying LBs generation causal triggers are still unknown. ɑ-Synuclein (ɑ-syn, encoded SNCA gene) is major component LBs, missense mutations duplications/triplications for rare hereditary forms PD. Thus, it imperative study ɑ-syn protein pathology, including oligomerization, fibril formation, aggregation, spreading mechanisms. Furthermore, there synergistic effects pathogenic mechanisms PD, multiple factors—contributing with different ratios—appear be progression factors. For example, oxidative stress, reduced antioxidative capacity, mitochondrial dysfunction, proteasomal disturbances each suggested formation aggregation contribute neuroinflammation neural cell death. Aging also risk factor Iron, well neuromelanin (NM), show age-dependent increases, iron significantly increased Parkinsonian substantia nigra (SN). Iron-induced include changes molecular structure ɑ-syn. more recent research demonstrates that (i) detected not only dopaminergic neurons glia but various neurotransmitter systems, (ii) sympathetic nerve fibres degenerate first, (iii) “brain-first” deficiency evident before induced NM. These findings support ɑ-syn/LBs iron- NM-induced important facts via their interaction potentiate process SN. As such, multifactorial toxic posted on personal genetic assumed neurodegenerative Differences ratios factors spatiotemporal development, fact common hard identify, imply existence several phenotypical subtypes, which supported arguments from both “bottom-up/dual-hit” models. Therapeutic strategies necessary avoid single initiation leading

Язык: Английский

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Revolutionizing our understanding of Parkinson’s disease: Dr. Heinz Reichmann’s pioneering research and future research direction

Journal of Neural Transmission, Год журнала: 2024, Номер 131(12), С. 1367 - 1387

Опубликована: Авг. 7, 2024

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, distinguished professor neurologist, has made substantial advancements in domain PD research, encompassing both fundamental scientific investigations practical applications. His research illuminated etiology treatment PD, as well function energy metabolism premotor symptoms. As precursor to number neurotransmitters neuromodulators that implicated pathophysiology he also investigated application tryptophan (Trp) derivatives disease. principal findings insights summarized synthesized this narrative review article, which emphasizes challenges implications for future research. This aims identify analyze key contributions Reichmann field ultimate goal informing directions domain. By examining Reichmann's work, study seeks provide comprehensive understanding his major how they can be applied advance diagnosis PD. paper explores potential intersection emerging avenues, such investigation Trp its metabolites, particularly kynurenines, could lead new therapeutic strategies managing disorders like

Язык: Английский

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Combating Parkinson’s Disease with Plant-Derived Polyphenols: Targeting Oxidative Stress and Neuroinflammation

Neurochemistry International, Год журнала: 2024, Номер 178, С. 105798 - 105798

Опубликована: Июнь 29, 2024

Язык: Английский

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