Mechanisms of Mitochondrial Malfunction in Alzheimer’s Disease: New Therapeutic Hope

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 28

Опубликована: Май 14, 2022

Mitochondria play a critical role in neuron viability or death as it regulates energy metabolism and cell pathways. They are essential for cellular metabolism, reactive oxygen species production, apoptosis, Ca++ homeostasis, aging, regeneration. Mitophagy mitochondrial dynamics thus processes the quality control of mitochondria. Improvements several fundamental features biology susceptible neurons AD brains putative underlying mechanisms such changes have made significant progress. AD’s etiology has been reported by malfunction oxidative damage. According to recent articles, continual fusion fission balance mitochondria is vital their normal function maintenance. As result, shape inextricably linked. This study examines evidence suggesting that dysfunction plays early impact on pathology. Furthermore, roles discussed with link between autophagy also explored. In addition, research mitophagy this review. It goes into how these flaws affect control. advanced therapy techniques lifestyle adjustments lead improved management demonstrated, hence improving conditions contribute AD.

Язык: Английский

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Discovering the Effects of Fisetin on NF-κB/NLRP-3/NRF-2 Molecular Pathways in a Mouse Model of Vascular Dementia Induced by Repeated Bilateral Carotid Occlusion

Biomedicines, Год журнала: 2022, Номер 10(6), С. 1448 - 1448

Опубликована: Июнь 19, 2022

Vascular dementia (VaD) is the second leading cause of dementia. The majority VaD patients have cognitive abnormalities, which are caused by cerebral hypoperfusion-induced ischemia, endothelial dysfunction, oxidative stress, and neuroinflammation. Natural products receiving increasing attention for treatment neuroinflammatory diseases. aim this study was to investigate molecular pathways underlying protective effects fisetin, a flavonoid present in many fruits vegetables, mouse model induced repeated ischemia-reperfusion (IR) total bilateral carotid artery. Here, we found that brain injury, lipid peroxidation, neuronal death hippocampus, as well astrocyte microglial activation, reduced BDNF neurotrophic factor expression together with behavioral alterations. In addition, activation inflammasome components (NLRP-3, ASC, caspase 1), their downstream (IL-1β IL-18) release promote apoptotic cell death. Fisetin attenuated histological malondialdehyde levels, pathway apoptosis, increased expression, astrocyte, deficits. conclusion, fisetin could be due inhibition ROS-induced NF-κB/NLRP3 antioxidant Nrf2/HO-1, suggesting possible crosstalk between these pathways.

Язык: Английский

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Sepsis-associated encephalopathy: From pathophysiology to clinical management

International Immunopharmacology, Год журнала: 2023, Номер 124, С. 110800 - 110800

Опубликована: Авг. 22, 2023

Язык: Английский

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Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5076 - 5076

Опубликована: Март 7, 2023

A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim this study was to evaluate beneficial effects fisetin, a naturally occurring polyphenol that frequently present in variety fruits vegetables. Uterine fragments were injected intraperitoneally cause endometriosis, fisetin given orally every day. At 14 days treatment, laparotomy performed, implants peritoneal fluids collected for histological, biochemical, molecular analyses. Rats subjected presented important macroscopic microscopic changes, increased mast cell (MC) infiltration, fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, volumes, well histological alterations, neutrophil cytokines release, number MCs together with expression chymase tryptase, diminished α smooth muscle actin (α-sma) transforming growth factor beta (TGF β) expressions. In addition, able reduce markers oxidative stress nitrotyrosine Poly ADP ribose expressions increase apoptosis lesions. conclusion, could represent new therapeutic strategy control perhaps targeting MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway stress.

Язык: Английский

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Fisetin orchestrates neuroinflammation resolution and facilitates spinal cord injury recovery through enhanced autophagy in pro-inflammatory glial cells

International Immunopharmacology, Год журнала: 2024, Номер 130, С. 111738 - 111738

Опубликована: Фев. 29, 2024

Язык: Английский

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ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Март 27, 2024

Язык: Английский

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Mitophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 10

Опубликована: Янв. 27, 2022

Traumatic brain injury (TBI) contributes to death, and disability worldwide more than any other traumatic insult damage cellular components including mitochondria leads the impairment of functions function. In neurons, mitophagy, autophagy-mediated degradation damaged mitochondria, is a key process in quality control mitochondrial homeostasis energy supply plays fundamental role neuronal survival health. Conversely, defective mitophagy accumulation dysfunction, contributing inflammation, oxidative stress, cell death. Therefore, an extensive characterization mitophagy-related protective mechanisms, taking into account complex mechanisms by which each molecular player connected others, may provide rationale for development new therapeutic strategies TBI patients. Here, we discuss contribution TBI, underlying death highlight novel therapeutics based on newly discovered mitophagy-inducing strategies.

Язык: Английский

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Mitophagy and Traumatic Brain Injury: Regulatory Mechanisms and Therapeutic Potentials

Oxidative Medicine and Cellular Longevity, Год журнала: 2023, Номер 2023, С. 1 - 15

Опубликована: Фев. 17, 2023

Traumatic brain injury (TBI), a kind of external trauma-induced function alteration, has posed financial burden on the public health system. TBI pathogenesis involves complicated set events, including primary and secondary injuries that can cause mitochondrial damage. Mitophagy, process in which defective mitochondria are specifically degraded, segregates degrades allowing healthier network. Mitophagy ensures remain healthy during TBI, determining whether neurons live or die. acts as critical regulator maintaining neuronal survival healthy. This review will discuss pathophysiology consequences damage it causes to mitochondria. article explore mitophagy process, its key factors, pathways reveal role TBI. be further recognized therapeutic approach offer new insights into mitophagy’s progression.

Язык: Английский

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Paediatric sepsis-associated encephalopathy (SAE): a comprehensive review

Molecular Medicine, Год журнала: 2023, Номер 29(1)

Опубликована: Фев. 23, 2023

Sepsis-associated encephalopathy (SAE) is one of the most common types organ dysfunction without overt central nervous system (CNS) infection. It associated with higher mortality, low quality life, and long-term neurological sequelae, its mortality in patients diagnosed sepsis, progressing to SAE, 9% 76%. The pathophysiology SAE still unknown, but mechanisms are well elaborated, including oxidative stress, increased cytokines proinflammatory factors levels, disturbances cerebral circulation, changes blood-brain barrier permeability, injury brain's vascular endothelium, altered levels neurotransmitters, amino acid microvascular cells, mitochondria dysfunction, activation microglia astrocytes, neuronal death. diagnosis involves excluding direct CNS infection or other encephalopathies, which might hinder early detection appropriate implementation management protocols, especially paediatric where only a few cases have been reported literature. commonly applied diagnostic tools include electroencephalography, imaging, biomarker detection. treatment mainly focuses on managing underlying conditions using antibiotics supportive therapy. In contrast, sedative medication used judiciously treat those showing features such as agitation. widely dexmedetomidine neuroprotective by inhibiting apoptosis reducing sepsis-associated inflammatory response, resulting improved short-term shorter time ventilator. Other agents, dexamethasone, melatonin, magnesium, also being explored vivo ex encouraging results. Managing modifiable crucial improving generalised outcomes. From mentioned above, there experimentation models strategies. Extrapolation adult challenging because evolving brain technical complexity model investigated. Here, we reviewed current understanding pathophysiological mechanisms, methods, therapeutic interventions, potential emerging agents.

Язык: Английский

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Nutrition and autophagy deficiency in critical illness

Current Opinion in Critical Care, Год журнала: 2023, Номер 29(4), С. 306 - 314

Опубликована: Июнь 8, 2023

Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to high risk multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. discusses insight into role autophagy in involvement artificial feeding insufficient activation Recent findings Animal studies manipulating have shown its protective effects against kidney, lung, liver, intestinal injury after several insults. also protected peripheral, respiratory, cardiac muscle despite aggravated atrophy. Its acute brain is more equivocal. patient showed that suppressed illness, particularly protein/amino acid doses. Feeding-suppressed may explain short long-term harm by early enhanced calorie/protein large randomized controlled trials. Summary Insufficient at least partly explained feeding-induced suppression. why nutrition failed benefit critically ill patients or even induced harm. Safe, specific avoiding prolonged starvation opens perspectives for improving outcomes

Язык: Английский

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