Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(10), P. 2439 - 2447

Published: March 1, 2022

Abstract Both mitochondrial dysfunction and neuroinflammation are implicated in neurodegeneration neurodegenerative diseases. Accumulating evidence shows multiple links between neuroinflammation. Mitochondrial-derived damage-associated molecular patterns (DAMPs) recognized by immune receptors of microglia aggravate On the other hand, inflammatory factors released activated glial cells trigger an intracellular cascade, which regulates metabolism function. The crosstalk neuroinflammatory activation is a complex dynamic process. There strong that precedes during progression Thus, in-depth understanding specific mechanisms associated with diseases may contribute to identification new targets for treatment In this review, we describe detail DAMPs induce or including mtDNA, unfolded protein response (mtUPR), reactive oxygen species (mtROS), adenosine triphosphate (ATP), transcription factor A mitochondria (TFAM), cardiolipin, cytochrome c , Ca 2+ iron.

Language: Английский

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Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114985 - 114985

Published: June 11, 2023

The gut microbiota is indispensable for maintaining host health by enhancing the host's digestive capacity, safeguarding intestinal epithelial barrier, and preventing pathogen invasion. Additionally, exhibits a bidirectional interaction with immune system promotes of to mature. Dysbiosis microbiota, primarily caused factors such as genetic susceptibility, age, BMI, diet, drug abuse, significant contributor inflammatory diseases. However, mechanisms underlying diseases resulting from dysbiosis lack systematic categorization. In this study, we summarize normal physiological functions symbiotic in healthy state demonstrate that when occurs due various external factors, are lost, leading pathological damage lining, metabolic disorders, barrier damage. This, turn, triggers disorders eventually causes systems. These discoveries provide fresh perspectives on how diagnose treat unrecognized variables might affect link between illnesses need further studies extensive basic clinical research will still be required investigate relationship future.

Language: Английский

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Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2607 - 2607

Published: Aug. 21, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently, growing preclinical studies have that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among others. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Language: Английский

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Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 231, P. 107988 - 107988

Published: Sept. 16, 2021

Language: Английский

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Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegenerative Disorders: Current Targets and Future Perspective

Current Neuropharmacology, Journal Year: 2021, Volume and Issue: 20(1), P. 158 - 178

Published: June 21, 2021

Neurodegenerative diseases are a group of pathological conditions that cause motor incordination (jerking movements), cognitive and memory impairments result from degeneration neurons in specific area the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation, neurochemical imbalance histone deacetylase enzymes (HDAC) known to play crucial role neurodegeneration. HDAC is classified into four categories (class I, II, III class IV) depending upon their location functions. HDAC1 2 involved neurodegeneration, while HDAC3-11 HDACs beneficial as neuroprotective. localized different parts brain- (hippocampus cortex), HDAC2 (nucleus), HDAC3, 4, 5, 7 9 (nucleus cytoplasm), HDAC6 & HDAC7 (cytoplasm) HDAC11 (Nucleus, cornus ammonis 1 spinal cord). In conditions, up-regulates glutamate, phosphorylation tau, glial fibrillary acidic proteins down-regulating BDNF, Heat shock protein 70 Gelsolin. Class divided seven sub-classes (SIRT1-SIRT7). Sirtuins brain neuron -Sirt1 Sirt2 (cortex, striatum, hippocampus cord), Sirt3 (mitochondria Sirt4, Sirt5 Sirt6 (mitochondria), Sirt7 (nucleus) Sirt8 (nucleolus). SIRTs (1, 3, 6) neuronal survival, proliferation modulating stress response, SIRT2 associated with Parkinsonism, Huntington's disease Alzheimer's disease, whereas SIRT6 only disease. this critical review, we have discussed mechanisms therapeutic targets would be for management neurodegenerative disorders.

Language: Английский

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β-Nicotinamide mononucleotide activates NAD+/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102745 - 102745

Published: May 13, 2023

Sepsis-associated encephalopathy (SAE) is one of the common serious complications in sepsis, and pathogenesis SAE remains unclear. Sirtuin 1 (SIRT1) has been reported to be downregulated hippocampus SIRT1 agonists can attenuated cognitive dysfunction septic mice. Nicotinamide adenine dinucleotide (NAD+) a key substrate maintain deacetylation activity SIRT1. As an intermediate NAD+, β-Nicotinamide Mononucleotide (NMN) promising treating neurodegenerative diseases cerebral ischemic injury. Thus we sought investigate potential role NMN treatment. The model was established by cecal ligation puncture (CLP) vivo, neuroinflammation with LPS-treated BV-2 cells vitro. Memory impairment assessed Morris water maze fear conditioning tests. result, levels PGC-1α were significantly reduced mice, while acetylation total lysine, phosphorylation P38 P65 enhanced. All these changes induced sepsis inverted NMN. Treating resulted improved behavior performance tests maze. Apoptosis, inflammatory oxidative responses mice after administration. These protective effect against memory dysfunction, injuries reversed inhibitor, EX-527. Similarly, LPS-induced activation NMN, EX-527 or knockdown could reverse such In conclusion, sepsis-induced region NAD+/SIRT1 pathway might involved mechanisms effect.

Language: Английский

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Unveiling the interplay of AMPK/SIRT1/PGC-1α axis in brain health: Promising targets against aging and NDDs

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102255 - 102255

Published: March 14, 2024

Language: Английский

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Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Jan. 25, 2024

Glaucoma is a neurodegenerative disease of the retina characterized by irreversible loss retinal ganglion cells (RGCs) leading to visual loss. Degeneration RGCs and their axons, as well damage remodeling lamina cribrosa are main events in pathogenesis glaucoma. Different molecular pathways involved RGC death, which triggered exacerbated consequence number risk factors such elevated intraocular pressure (IOP), age, ocular biomechanics, or low perfusion pressure. Increased IOP one most important associated with this pathology only for treatment currently available, nevertheless, on many cases progression continues, despite control. Thus, elevation not trigger glaucomatous damage, showing evidence that other can induce death pathology, would be advance neurodegeneration. The underlying mechanisms driving process glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress neuroinflammation. In glaucoma, like disorders, immune system immunoregulation conducted mainly glial cells, microglia, astrocytes, Müller cells. increase produces activation tissue. Chronic may provoke proinflammatory state at level inducing blood barrier disruption death. modulation response constitute an interesting new approach

Language: Английский

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Calycosin‑7‑O‑β‑D‑glucoside downregulates mitophagy by mitigating mitochondrial fission to protect HT22 cells from oxygen‑glucose deprivation/reperfusion‑induced injury

Molecular Medicine Reports, Journal Year: 2025, Volume and Issue: 31(3)

Published: Jan. 13, 2025

Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the CG are associated with mitochondrial protection remains unclear. The present study explored role in improving function HT22 cell model oxygen‑glucose deprivation/reperfusion (OGD/R). Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate on function. results demonstrated that was restored after treatment CG, as indicated by reduced reactive oxygen species levels, increased membrane potential improved morphology. Overactivated mitophagy revealed be inhibited regulation proteins involved fission [phosphorylated‑dynamin‑related protein 1 (Drp1) Drp1] (LC3, p62 translocase outer 20), biogenesis enhanced levels sirtuin (SIRT1) peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis ameliorated determined decreased rate apoptosis, caspase‑3 Bcl‑2/Bax. conclusion, may alleviate OGD/R‑induced injury upregulating SIRT1 PGC‑1α expression, reducing excessive overactivation mitophagy.

Language: Английский

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Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice

Aging, Journal Year: 2020, Volume and Issue: 12(7), P. 6401 - 6414

Published: April 8, 2020

The natural polyamine spermidine and spermine have been reported to ameliorate aging aging-induced dementia.However, the mechanism is still confused.An model, senescence accelerated mouse-8 (SAMP8), was used in this study.Novel object recognition open field test results showed that oral administration of spermidine, rapamycin increased discrimination index, modified number, inner squares distance times.Spermidine activity SOD, decreased level MDA brain.Spermidine phosphorylate AMPK regulate autophagy proteins (LC3, Beclin 1 p62).Spermidine balanced mitochondrial maintain energy for neuron, with regulation MFN1, MFN2, DRP1, COX IV ATP.In addition, western blot (Bcl-2, Bax Caspase-3, NLRP3, IL-18, IL-1β) prevented apoptosis inflammation, elevate expression neurotrophic factors, including NGF, PSD95and PSD93 BDNF neurons SAMP8 mice.These indicated effect on anti-aging related improving function.

Language: Английский

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