Editorial: The (un)desirability of cell death in health and disease: emerging modulators and their mechanisms DOI Creative Commons
Daniel José Barbosa, Joana Barbosa, Elaine M. Souza–Fagundes

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 19, 2024

Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal. *Correspondence: Patrícia M. A. Silva ([email protected])The balanced regulation of cell death and survival is critical for maintaining the homeostasis human body. Disruption this delicate equilibrium often underlies development several diseases. For instance, cancer cells develop resistance to natural mechanisms, leading uncontrolled proliferation malignant growth (1,2). Conversely, neurodegenerative diseases involve progressive loss specific brain populations, resulting in a broad spectrum debilitating symptoms and, ultimately, (3, 4) (Figure 1).The incidence prevalence both are rising rapidly, significantly impacting patients' quality life creating major economic healthcare challenges worldwide (5,6). While knowledge about role abnormal these has advanced, precise mechanisms driving processes, as well effective strategies modulate them, remain only partially understood. This limited understanding complicates efforts tailor treatments different disease types. cancer, therapeutic approaches focus on inducing eliminate cells, whereas diseases, goal shifts preventing preserve affected neurons delay symptom progression. Research Topic focused enriching our emerging modulators death, exploring their action potential applications various scenarios.In total, two original research articles three review were published. editorial briefly summarizes findings highlights key insights derived from articles, emphasizing contributions field they present guiding future and/or strategies. release ALL dependent Gαi subunit, its inhibition blocks process without affecting Gβϒ. Moreover, further experiments showed that activating adenylyl cyclase (AC) with forskolin or using 8-CPT-cAMP inhibits D,L-methadone-induced ER Ca 2+ release, suggesting Gαi-mediated downregulation AC cAMP. Notably, protein kinase A (PKA) inhibitor 14-22 amide (myr) can independently elicit

Language: Английский

Polyphenols, Alkaloids, and Terpenoids Against Neurodegeneration: Evaluating the Neuroprotective Effects of Phytocompounds Through a Comprehensive Review of the Current Evidence DOI Creative Commons

Enzo Pereira de Lima,

Lucas Fornari Laurindo,

Vitor Cavallari Strozze Catharin

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(2), P. 124 - 124

Published: Feb. 13, 2025

Neurodegenerative diseases comprise a group of chronic, usually age-related, disorders characterized by progressive neuronal loss, deformation structure, or loss function, leading to substantially reduced quality life. They remain significant focus scientific and clinical interest due their increasing medical social importance. Most neurodegenerative present intracellular protein aggregation extracellular deposition (plaques), such as α-synuclein in Parkinson's disease amyloid beta (Aβ)/tau aggregates Alzheimer's. Conventional treatments for conditions incur high costs are related the development several adverse effects. In addition, many patients irresponsive them. For these reasons, there is growing tendency find new therapeutic approaches help patients. This review intends investigate some phytocompounds' effects on diseases. These generally increased oxidative stress inflammation, so phytocompounds can prevent treat To achieve our aim provide critical assessment current literature about phytochemicals targeting neurodegeneration, we reviewed reputable databases, including PubMed, EMBASE, COCHRANE, seeking trials that utilized against conditions. A few investigated humans, after screening, 13 were ultimately included following PRISMA guidelines. compounds include polyphenols (flavonoids luteolin quercetin, phenolic acids rosmarinic acid, ferulic caffeic other like resveratrol), alkaloids (such berberine, huperzine A, caffeine), terpenoids ginkgolides limonene). The gathered evidence underscores caffeine, ginkgolides, primarily anti-inflammatory, antioxidant, neuroprotective, counteracting neuroinflammation, oxidation, synaptic dysfunctions, which crucial aspects intervention various conditions, Alzheimer's dementias, depression, neuropsychiatric disorders. summary, they show use improvements cognition, memory, disinhibition, irritability/lability, aberrant behavior, hallucinations, mood

Language: Английский

Citations

7
The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization DOI Open Access
Evgeniya I. Fedotova, Alexey V. Berezhnov, Daniil Y. Popov

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1019 - 1019

Published: Jan. 25, 2025

Atherosclerosis is a complex inflammatory process associated with high-mortality cardiovascular diseases. Today, there growing body of evidence linking atherosclerosis to mutations mitochondrial DNA (mtDNA). But the mechanism this link insufficiently studied. progression involves different cell types and macrophages are one most important. Due their high plasticity, can demonstrate pro-inflammatory pro-atherogenic (macrophage type M1) or anti-inflammatory anti-atherogenic M2) effects. These two types, formed as result external stimuli, differ significantly in metabolic profile, which suggests central role mitochondria implementation macrophage polarization route. According this, we assume that mtDNA causing disturbances play an internal trigger, leading formation M1 M2. This review provides comparative analysis characteristics function possible associations linked inflammation-based pathologies including atherosclerosis.

Language: Английский

Citations

2
Cyclophilin D (CypD) ablation prevents neurodegenerative and cognitive damage induced by caspase-3 cleaved tau. DOI

Margrethe A. Olesen,

Francisca Villavicencio-Tejo,

Gail V.W. Johnson

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus DOI
Yogesh Mishra, Ashutosh Kumar, Ravinder K. Kaundal

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Language: Английский

Citations

6
Interplay of mitochondrial calcium signalling and reactive oxygen species production in the brain DOI Creative Commons

Plamena R. Angelova,

Andrey Y. Abramov

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(4), P. 1939 - 1946

Published: Aug. 22, 2024

Intracellular communication and regulation in brain cells is controlled by the ubiquitous Ca2+ redox signalling. Both of these independent signalling systems regulate most processes including cell surviving mechanism or death. In physiology can trigger reactive oxygen species (ROS) production various enzymes mitochondria but ROS could also transmit signal to calcium levels via modification channels phospholipase activity. Changes lead severe pathology resulting excitotoxicity oxidative stress. Interaction essential opening mitochondrial permeability transition pore - initial step apoptosis, ROS-induced stress involved necrosis ferroptosis. Here we review role cytosol neurons astrocytes how this integration pathology, ischaemia injury neurodegeneration.

Language: Английский

Citations

6
Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability DOI Creative Commons
Wen Xie, Sushruta Koppula, Mayur B. Kale

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 5, 2024

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible energy production and calcium regulation. This review offers an in-depth examination of interplay between epilepsy, mitochondrial function, aging. Many factors might account correlation epilepsy Mitochondria, integral to dynamics neuronal excitability, perform critical role in pathophysiology epilepsy. The mechanisms linking mitochondria are multifaceted, involving dysfunction, reactive oxygen species (ROS), dynamics. Mitochondrial dysfunction can trigger seizures compromising ATP production, increasing glutamate release, altering ion channel function. ROS, natural byproducts respiration, contribute oxidative stress neuroinflammation, epileptogenesis. govern fusion fission processes, influence seizure threshold buffering, impact propagation. Energy demands during highlight generation maintaining membrane potential. handling dynamically modulates affecting synaptic transmission action potential generation. Dysregulated hallmark contributing excitotoxicity. Epigenetic modifications function through histone modifications, DNA methylation, non-coding RNA expression. Potential therapeutic avenues targeting include mitochondria-targeted antioxidants, ketogenic diets, metabolic therapies. concludes outlining future directions research, emphasizing integrative approaches, advancements ethical considerations. Mitochondria emerge as central players narrative offering profound insights this challenging disorder.

Language: Английский

Citations

6
Point of No Return—What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death DOI Creative Commons
Kristina A. Kritskaya, Olga Stelmashchuk, Andrey Y. Abramov

et al.

Journal of Cellular Physiology, Journal Year: 2025, Volume and Issue: 240(1)

Published: Jan. 1, 2025

Programmed cell death (apoptosis) is essential part of the process tissue regeneration that also plays role in mechanism pathology. The phenomenon fast and transient permeability mitochondrial membranes by various triggers, known as transition pore (mPTP) leads to release proapoptotic proteins acts an initial step initiation apoptosis. However, a for mPTP was suggested physiology it unclear if there threshold number mitochondria with which induces how this regulated different tissues. Using simultaneous measurements membrane potential fluorescent marker caspase-3 activation we studied calcium-induced opening necessary induction apoptosis rat primary cortical neurons, astrocytes, fibroblasts, cancer (BT-474) cells. correlated 80%-90% signal loss neural cells but only 35% BT-474 over 90% opens before becomes obvious. induce did not correlate total expression levels consistent Bax/Bcl-2 ratio these Calcium-induced increased necrosis higher fibroblasts compared astrocytes Thus, tissues require specific numbers PTP correlates proapoptotic/antiapoptotic them.

Language: Английский

Citations

0
Early Synapse-Specific Alterations of Photoreceptor Mitochondria in the EAE Mouse Model of Multiple Sclerosis DOI Creative Commons

Dalia Ibrahim,

Karin Schwarz,

Shweta Suiwal

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 206 - 206

Published: Jan. 30, 2025

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) linked to many neurological disabilities. The visual frequently impaired in MS. In previous studies, we observed early malfunctions rod photoreceptor ribbon synapses EAE mouse model MS that included alterations synaptic vesicle cycling and disturbances presynaptic Ca2+ homeostasis. Since these events are highly energy-demanding, analyzed whether mitochondria, which play a major role energy metabolism, might be involved at stage. Rod terminals contain single large mitochondrion next ribbon. present study, expression functionally relevant mitochondrial proteins (MIC60, ATP5B, COX1, PINK1, DRP1) by high-resolution qualitative quantitative immunofluorescence microscopy, immunogold electron microscopy Western blot experiments. We decreased mitochondria photoreceptors stage, suggesting dysfunctions important synapse pathology. Interestingly, were strongly compromised EAE, whereas extra-synaptic inner segments remained unchanged, demonstrating functional heterogeneity mitochondria.

Language: Английский

Citations

0
Anti-inflammatory and antioxidant effects of baicalein: targeting Nrf2, and NFĸB in neurodegenerative disease DOI

Omkar Kumar Kuwar,

Neena Kalia

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

Citations

0
Comparative Study of Structural and Functional Rearrangements in Skeletal Muscle Mitochondria of SOD1-G93A Transgenic Mice at Pre-, Early-, and Late-Symptomatic Stages of ALS Progression DOI Creative Commons
Natalia V. Belosludtseva, Anna I. Ilzorkina, Mikhail V. Dubinin

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(3)

Published: March 18, 2025

Background: Amyotrophic lateral sclerosis (ALS) is a progressive multisystem disease characterized by limb and trunk muscle weakness that attributed, in part, to abnormalities mitochondrial ultrastructure impaired functions. This study investigated the time course of structural functional rearrangements skeletal mitochondria combination with motor impairments Tg (copper-zinc superoxide dismutase enzyme (SOD1) G93A) dl1/GurJ (referred as SOD1-G93A/low) male mice, familial ALS model, compared non-transgenic littermates. Methods: The neurological status functions were assessed weekly using paw grip endurance method grid suspension test two-limb four-limb tasks. Transmission electron microscopy followed quantitative analysis was performed ultrastructural alterations quadriceps femoris. Functional high-resolution Oxygraph-2k (O2K) respirometry methods for assessing calcium retention capacity index content lipid peroxidation products freshly isolated preparations. Results: Based on behavioral phenotyping data, specific age groups identified: postnatal day 56 (P56) (n = 10–11), 84 (P84) 156 (P154) 10–12), representing pre-symptomatic, early-symptomatic late-symptomatic stages progression SOD1-G93A/low respectively. Electron showed mosaic destructive changes subsarcolemmal fibers femoris from 84-day-old mice. Morphometric revealed an elevation mean size SOD1-G93A mice at P84 P154. In addition, P154 transgenic group demonstrated decrease sarcomere width number per unit area. At symptomatic stage, exhibited decreased respiratory control ratio, ADP-stimulated, uncoupled respiration rates muscle, measured respirometry. parallel, lower increased levels control. Conclusions: Taken together, these results indicate stage-dependent associated defective oxidative phosphorylation, homeostasis, damage mouse which appears be promising direction development therapies ALS.

Language: Английский

Citations

0