Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: July 23, 2023

Abstract Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, multiple ischemic stroke, traumatic brain injury, spinal cord viral encephalitis, bacterial encephalitis. Microglia astrocytes are essential neural development, maintenance synaptic connections, homeostasis a healthy brain. The activation microglia is defense mechanism against damaged tissues harmful pathogens. However, their triggers neuroinflammation, which can exacerbate or induce CNS injury. Non-coding RNAs (ncRNAs) functional RNA molecules that lack coding capabilities but actively regulate mRNA expression function through various mechanisms. ncRNAs highly expressed potential mediators neuroinflammation. We reviewed recent research progress on role miRNAs, lncRNAs, circRNAs regulating neuroinflammation diseases. Understanding how these affect will provide important therapeutic insights for preventing managing dysfunction.

Language: Английский

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Nitric Oxide in Parkinson’s Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate–Nitrite–Nitric Oxide Pathway

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 393 - 393

Published: Jan. 22, 2025

Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks PD include Lewy bodies mechanisms like oxidative/nitrosative stress, chronic inflammation, mitochondrial dysfunction. Nitric oxide (NO), produced nitric synthase (NOS) isoforms, plays dual role neuroprotection neurodegeneration. Excessive NO production exacerbates neuroinflammation damage, contributing cell death. This review explores NO’s pathogenesis investigates dietary nitrate therapeutic strategy regulate levels. Methods: A literature studies addressing was conducted using major scientific databases, including PubMed, Scopus, Web Science, keywords “nitric oxide”, “NOSs”, “Parkinson’s disease”, “nitrate PD”. Studies on metabolism via nitrate–nitrite–NO pathway its effects were analyzed. regarding nitrosamine formation PD, which are mainly formed during nitrification process amines (nitrogen-containing compounds), often due chemical reactions presence nitrite or nitrate, also examined. In particular, has been shown induce oxidative affect function, contribute inflammatory phenomena brain, another factor closely related PD. Results: production, particularly from iNOS nNOS, strongly associated with amplifying neuronal damage Dietary enhance bioavailability through pathway, mitigating inflammation damage. Conclusions: Dysregulated contributes significantly progression pathways. modulating levels, offers promising counteract these mechanisms. Further clinical trials warranted establish efficacy optimize use management.

Language: Английский

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DNA Damage and Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4187 - 4187

Published: April 10, 2024

The etiology underlying most sporadic Parkinson's' disease (PD) cases is unknown. Environmental exposures have been suggested as putative causes of the disease. In cell models and in animal studies, certain chemicals can destroy dopaminergic neurons. However, mechanisms how these cause death neurons not understood. Several agents are mitochondrial toxins that inhibit complex I electron transport chain. Familial PD genes also encode proteins with important functions mitochondria. Mitochondrial dysfunction respiratory chain, combination presence redox active dopamine molecules cells, will lead to accumulation reactive oxygen species (ROS) Here, propose a mechanism regarding ROS may killing specificity for One rarely considered hypothesis produced by defective mitochondria formation oxidative DNA damage nuclear DNA. Many neuron-specific extraordinary long, ranging size from several hundred kilobases well over megabase. It predictable such long contain large numbers damaged bases, example form 8-oxoguanine (8-oxoG), which major type ROS. These lesions slow down or stall progression RNA polymerase II, term referred transcription stress. Furthermore, ROS-induced mutations, even postmitotic cells impaired mutagenesis loss neuronal integrity, eventually leading during human lifetime.

Language: Английский

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Ca2+ signalling: A common language for organelles crosstalk in Parkinson's disease

Cell Calcium, Journal Year: 2023, Volume and Issue: 115, P. 102783 - 102783

Published: July 27, 2023

Parkinson's disease (PD) is a neurodegenerative caused by multifactorial pathogenic mechanisms. Familial PD linked with genetic mutations in genes whose products are either associated mitochondrial function or endo-lysosomal pathways. Of note, mitochondria essential to sustain high energy demanding synaptic activity of neurons and alterations Ca2+ signaling have been proposed as causal events for process, although the mechanisms responsible selective loss specific neuronal populations different diseases still not clear. Here, we specifically discuss importance correct communication other organelles occurring at regions where their membranes become close contact. We nature role contact sites that establish ER, lysosomes, peroxisomes, how related proteins participate regulation/dysregulation tethering complexes. Unravelling molecular details could contribute identify therapeutic targets develop new strategies counteract progression disease.

Language: Английский

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Novel Insights into Parkin–Mediated Mitochondrial Dysfunction and “Mito-Inflammation” in α-Synuclein Toxicity. The Role of the cGAS–STING Signalling Pathway

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 4549 - 4574

Published: July 1, 2024

Abstract: The prevalence of age-related neurodegenerative diseases, such as Parkinson's disease (PD) and related disorders continues to grow worldwide. Increasing evidence links intracellular inclusions misfolded alpha-synuclein (α-syn) aggregates, so-called Lewy bodies (LB) neuritis, the progressive pathology PD other synucleinopathies. Our previous findings established that α-syn oligomers induce S-nitrosylation deregulation E3-ubiquitin ligase Parkin, leading mitochondrial disturbances in neuronal cells. accumulation damaged mitochondria a consequence, together with release mitochondrial-derived damage-associated molecular patterns (mtDAMPs) could activate innate immune response neuroinflammation ("mito-inflammation"), eventually accelerating neurodegeneration. However, pathways transmit pro-inflammatory signals from are not well understood. One proposed be cyclic GMP-AMP synthase (cGAS) – stimulator interferon genes (STING) (cGAS–STING) pathway, which plays pivotal role modulating response. It has recently been suggested cGAS–STING may contribute development various pathological conditions. Especially, its excessive engagement lead appear essential for brain including PD. precise mechanisms underlying pathway activation synucleinopathies fully This review focuses on linking dysfunction these disorders, particularly emphasizing signaling. We propose critical driver inflammation α-syn-dependent neurodegeneration hypothesize cGAS–STING–driven "mito-inflammation" one key promoting Understanding α-syn–induced cGAS–STING–associated identification new targets treatment disorders. Keywords: α-synuclein, mtDAMPs, mito-inflammation, sterile inflammation,

Language: Английский

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Parkin-mediated mitophagy protects against aluminum trichloride-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 264, P. 115459 - 115459

Published: Sept. 11, 2023

Aluminum is a neurotoxic food contaminant. trichloride (AlCl3) causes hippocampal mitochondrial damage, leading to injury. Damaged mitochondria can release reactive oxygen species (mtROS) and activate nucleotide-binding oligomerization domain-like receptor-containing 3 (NLRP3) inflammasomes apoptosis. E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy attenuate damage. However, the role of in AlCl3-induced mice damage its regulatory mechanism remain elusive. First, C57BL/6 N were treated with 0, 44.825, 89.65, 179.3 mg/kg body weight AlCl3 drinking water for 90 d. Apoptosis, NLRP3-inflammasome activation increased In addition, Parkin-mediated peaked middle-dose group was slightly attenuated high-dose group. Subsequently, we used wild-type Parkin knockout (Parkin-/-) investigate The results showed that Parkin-/- inhibited mitophagy, aggravated activation, apoptosis Finally, administered MitoQ (mtROS inhibitor) MCC950 (NLRP3 AlCl3-treated mitophagy. inhibition mtROS NLRP3 apoptosis, mice. These findings indicate protects against via mtROS-NLRP3 pathway.

Language: Английский

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Pterostilbene attenuates oxidative stress induced by hydrogen peroxide in MAC-T cells through activating PINK1/Parkin-mediated mitophagy

Italian Journal of Animal Science, Journal Year: 2024, Volume and Issue: 23(1), P. 758 - 768

Published: May 17, 2024

High‐producing dairy cows are susceptible to altered redox balance owing their high secretion and strong metabolism during transition lactation. Previously reports demonstrated that pterostilbene (PTE) alleviate hydrogen peroxide (H2O2)-induced oxidative damage. However, molecular mechanism underlying protective role of PTE in H2O2-elicited stress bovine mammary epithelial cells (MAC-T cells) remains unclear. The aims our research is clarify the potential mechanisms H2O2-triggered MAC-T were pre-treated with (0, 10, 25 50 μM) for 12 h then cultured H2O2 100, 200, 400, 600, 800 1000 another 24 h. results interpreted by CCK8, western blot, immunofluorescence assay. Results showed significantly attenuated H2O2-mediated reduction T-AOC, SOD GSH-Px activity. Mechanistic studies found restricted H2O2-induced protein expression HO-1, GPX4 SOD1, reversed intracellular MDA ROS generation decreased MMP cells. Moreover, exposure markedly inhibited mitophagy, whereas pre-treatment activated PINK1/Parkin-mediated mitophagy pathway, which further limited production. Overall, can be used improve as a novel antioxidant agent cows.

Language: Английский

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Targeting protein interaction networks in mitochondrial dynamics for neurodegenerative diseases

Journal of Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 15(3), P. 309 - 328

Published: July 5, 2024

Language: Английский

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Glycolic acid and D-lactate—putative products of DJ-1—restore neurodegeneration in FUS - and SOD1-ALS

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(8), P. e202302535 - e202302535

Published: May 17, 2024

Amyotrophic lateral sclerosis (ALS) leads to death within 2–5 yr. Currently, available drugs only slightly prolong survival. We present novel insights into the pathophysiology of Superoxide Dismutase 1 (SOD1)- and in particular Fused In Sarcoma (FUS)-ALS by revealing a supposedly central role glycolic acid (GA) D-lactic (DL)—both putative products Parkinson’s disease associated glyoxylase DJ-1. Combined, not single, treatment with GA/DL restored axonal organelle phenotypes mitochondria lysosomes FUS- SOD1-ALS patient-derived motoneurons (MNs). This was accompanied restoration mitochondrial membrane potential but even dependent on it. Despite presenting an transport deficiency as well, TDP43 MNs did share depolarization respond treatment. GA DL also cytoplasmic mislocalization FUS recruitment DNA damage sites, recently reported being upstream FUS-ALS. Whereas these data point towards necessity individualized (gene-) specific therapy stratification, it suggests common therapeutic targets across different neurodegenerative diseases characterized depolarization.

Language: Английский

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Mechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Nov. 28, 2024

Language: Английский

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