Astrocytic pathology in Alpers’ syndrome DOI Creative Commons
Laura A. Smith, Chun Chen,

Nichola Z. Lax

и другие.

Acta Neuropathologica Communications, Год журнала: 2023, Номер 11(1)

Опубликована: Май 31, 2023

Abstract Refractory epilepsy is the main neurological manifestation of Alpers’ syndrome, a severe childhood-onset mitochondrial disease caused by bi-allelic pathogenic variants in DNA (mtDNA) polymerase gamma gene ( POLG ). The pathophysiological mechanisms underpinning neuronal hyperexcitabilty leading to seizures syndrome remain unknown. However, pathological changes reactive astrocytes are hypothesised exacerbate neural dysfunction and seizure-associated cortical activity POLG-related disease. Therefore, we sought phenotypically characterise astrocytic pathology syndrome. We performed detailed quantitative investigation post-mortem neocortical tissues from thirteen patients with eight neurologically normal controls five sudden unexpected death (SUDEP) patients, control for generalised epilepsy-associated pathology. Immunohistochemistry identify glial fibrillary acidic protein (GFAP)-reactive revealed striking astrogliosis localised primary visual cortex tissues, characterised abnormal-appearing hypertrophic astrocytes. Phenotypic characterisation individual GFAP-reactive demonstrated decreased abundance oxidative phosphorylation (OXPHOS) proteins altered expression key including Kir4.1 (subunit inwardly rectifying K + ion channel), AQP4 (astrocytic water channel) glutamine synthetase (enzyme that metabolises glutamate). These phenotypic were typically different observed SUDEP suggesting alternative between these epilepsies. Crucially, our findings provide further evidence occipital lobe involvement support pathogenesis

Язык: Английский

Connecting Dots between Mitochondrial Dysfunction and Depression DOI Creative Commons

Mehtab Khan,

Yann Baussan,

Étienne Hébert-Chatelain

и другие.

Biomolecules, Год журнала: 2023, Номер 13(4), С. 695 - 695

Опубликована: Апрель 20, 2023

Mitochondria are the prime source of cellular energy, and also responsible for important processes such as oxidative stress, apoptosis Ca2+ homeostasis. Depression is a psychiatric disease characterized by alteration in metabolism, neurotransmission neuroplasticity. In this manuscript, we summarize recent evidence linking mitochondrial dysfunction to pathophysiology depression. Impaired expression mitochondria-related genes, damage membrane proteins lipids, disruption electron transport chain, higher neuroinflammation all observed preclinical models depression most these parameters can be altered brain patients with A deeper knowledge identification phenotypes biomarkers respect needed help early diagnosis development new treatment strategies devastating disorder.

Язык: Английский

Процитировано

29
Mitochondrial fission and fusion in neurodegenerative diseases:Ca2+ signalling DOI
Xuan Liu, Tianjiao Li, Xiaoming Tu

и другие.

Molecular and Cellular Neuroscience, Год журнала: 2025, Номер unknown, С. 103992 - 103992

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Язык: Английский

Процитировано

1
Mitochondrial Dysfunction: At the Nexus between Alcohol-Associated Immunometabolic Dysregulation and Tissue Injury DOI Open Access
Robert W. Siggins, Patrick M. McTernan, Liz Simon

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(10), С. 8650 - 8650

Опубликована: Май 12, 2023

Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such ATP synthesis initiation apoptosis. However, current research has provided evidence that mitochondria participate myriad cellular processes, immune activation, nutrient sensing pancreatic β-cells, muscle stem progenitor cell differentiation. The literature indicates alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation disrupting dynamics, leading to dysfunctional accumulation. As discussed this review, dyshomeostasis emerges at nexus between alcohol-disrupted tissue injury. Here, we highlight link focus on alcohol-mediated disruption immunometabolism, which refers two distinct, yet interrelated processes. Extrinsic immunometabolism involves processes whereby cells products influence and/or metabolism. Intrinsic describes fuel utilization bioenergetics affect intracellular Alcohol-induced dysregulation cells, contributing This review will present state literature, describing metabolic immunometabolic from perspective.

Язык: Английский

Процитировано

17
A comprehensive perspective of Huntington’s disease and mitochondrial dysfunction DOI Creative Commons

Yinghong Dai,

Haonan Wang, Aojie Lian

и другие.

Mitochondrion, Год журнала: 2023, Номер 70, С. 8 - 19

Опубликована: Март 10, 2023

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. It caused by the expansion of CAG trinucleotide repeat sequence in HTT gene. HD mainly manifests as involuntary dance-like movements and severe mental disorders. As it progresses, patients lose ability to speak, think, even swallow. Although pathogenesis unclear, studies have found that mitochondrial dysfunctions occupy important position HD. Based on latest research advances, this review sorts out discusses role dysfunction terms bioenergetics, abnormal autophagy, membranes. This provides researchers with a more complete perspective mechanisms underlying relationship between dysregulation

Язык: Английский

Процитировано

16
Epilepsy: Mitochondrial connections to the ‘Sacred’ disease DOI Creative Commons
Walter H. Moos, Douglas V. Faller,

Ioannis P. Glavas

и другие.

Mitochondrion, Год журнала: 2023, Номер 72, С. 84 - 101

Опубликована: Авг. 13, 2023

Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms epilepsy makes diagnosis challenging. Diagnosis and monitoring childhood add to the need non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms epileptogenesis are not fully understood, evidence mitochondrial involvement is substantial. Seizures affect 35%-60% patients diagnosed with diseases. Mitochondrial dysfunction pathophysiological in various epilepsies, including those non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads altered neuronal bioenergetics, metabolism neurological complications, Iron-dependent lipid peroxidation initiates ferroptosis, a death pathway that aligns morphology found neurodegenerative diseases (NDDs). Studies mouse genetic models seizure phenotypes where function an essential selenoprotein (GPX4) targeted suggest roles ferroptosis epilepsy. GPX4 pivotal NDDs, selenium protects interneurons ferroptosis. Selenium central nervous system micronutrient trace element. Low serum concentrations other elements minerals, iron, noted diagnosing supplements alleviate intractable seizures children reduced GPX activity. Copper cuproptosis, like iron link NDDs. Connecting these mechanistic pathways selenoproteins provides new insights into treating seizures, pointing using medicines prodrugs lipoic acid treat potential alternative therapeutic approaches transcranial magnetic stimulation (transcranial), photobiomodulation vagus nerve stimulation.

Язык: Английский

Процитировано

16
Mitochondria in Mesenchymal Stem Cells: Key to Fate Determination and Therapeutic Potential DOI
Yang Liu, Lingjuan Wang, Jihui Ai

и другие.

Stem Cell Reviews and Reports, Год журнала: 2024, Номер 20(3), С. 617 - 636

Опубликована: Янв. 24, 2024

Язык: Английский

Процитировано

6
Mapping stress-responsive signaling pathways induced by mitochondrial proteostasis perturbations DOI
Nicole Madrazo, Zinia Khattar, Evan T. Powers

и другие.

Molecular Biology of the Cell, Год журнала: 2024, Номер 35(5)

Опубликована: Март 27, 2024

Imbalances in mitochondrial proteostasis are associated with pathologic dysfunction implicated etiologically diverse diseases. This has led to considerable interest defining the mechanisms responsible for regulating mitochondria response stress. Numerous stress-responsive signaling pathways have been suggested regulate proteotoxic These include integrated stress (ISR), heat shock (HSR), and oxidative (OSR). Here, we define activated chronic perturbations by monitoring expression of sets genes regulated downstream each these published Perturb-seq datasets from K562 cells CRISPRi-depleted factors. Interestingly, find that ISR is preferentially chronic, genetically-induced stress, no other pathway showing significant activation. Further, demonstrate CRISPRi depletion mitochondria-localized proteins similarly shows preferential activation relative pathways. results both establish our gene set profiling approach as a viable strategy probe responsive induced specific organelles identify predominant disruption proteostasis.

Язык: Английский

Процитировано

6
Advancements in the study of synaptic plasticity and mitochondrial autophagy relationship DOI
Yousong Zhu,

Qinlong Hui,

Zheng Zhang

и другие.

Journal of Neuroscience Research, Год журнала: 2024, Номер 102(2)

Опубликована: Фев. 1, 2024

Abstract Synapses serve as the points of communication between neurons, consisting primarily three components: presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through release reception neurotransmitters. Synaptic plasticity, ability synapses to undergo structural functional changes, is influenced by proteins such growth‐associated proteins, vesicle density neurotrophic growth factors. Furthermore, maintaining plasticity consumes more than half brain's energy, with a significant portion this energy originating from ATP generated mitochondrial metabolism. Consequently, quantity, distribution, transport, function mitochondria impact stability brain metabolism, thereby participating in regulation fundamental processes including neuronal differentiation, neurite outgrowth, synapse formation, neurotransmitter release. This article provides comprehensive overview associated common factors two, well relationship metabolism plasticity.

Язык: Английский

Процитировано

5
Cerium Vanadate Nanozyme with pH-Dependent Dual Enzymatic Activity for Glioblastoma Targeted Therapy and Postradiotherapy Damage Protection DOI Creative Commons
Xiao Han, Boyan Li, Wenhan Wang

и другие.

ACS Nano, Год журнала: 2024, Номер unknown

Опубликована: Июль 17, 2024

Nanocatalytic therapy is an emerging technology that uses synthetic nanoscale enzyme mimics for biomedical treatment. However, in the field of neuroscience, achieving neurological protection while simultaneously killing tumor cells a technical challenge. Herein, we synthesized biomimic and translational cerium vanadate (CeVO4) nanozyme glioblastoma (GBM) repair brain damage after GBM ionizing radiation (IR). This system exhibited pH dependence: it showed potent Superoxide dismutase (SOD) activity neutral environment Peroxidase (POD) acidic environment. In cells, this acted lysosomes, causing cellular reactive oxygen species (ROS) accumulation; neuronal could undergo lysosomal escape aggregation with mitochondria, reversing mitochondrial caused by IR restoring expression level antiapoptotic BCL-2 protein. Mechanistically, believe distribution difference related to specific uptake internalization mechanism pathway neurons, ultimately led dual effect nerve vivo model. summary, study provides insight into therapy.

Язык: Английский

Процитировано

5