Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113681 - 113681

Published: Jan. 21, 2024

Mitochondrial calcium (Ca2+) uptake augments metabolic processes and buffers cytosolic Ca2+ levels; however, excessive mitochondrial can cause cell death. Disrupted function homeostasis are linked to numerous neurodegenerative diseases (NDs), but the impact of disruption is not well understood. Here, we show that Drosophila models multiple NDs (Parkinson's, Huntington's, Alzheimer's, frontotemporal dementia) reveal a consistent increase in neuronal levels, as reduced buffering capacity, associated with increased mitochondria-endoplasmic reticulum contact sites (MERCs). Importantly, loss channel MCU or overexpression efflux NCLX robustly suppresses key pathological phenotypes across these ND models. Thus, imbalance common feature diverse vivo an important contributor disease pathogenesis. The broad beneficial effects from partial presents common, druggable target for therapeutic intervention.

Language: Английский

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Mitochondrial Dysfunction and Metabolic Reprogramming in Obesity and Asthma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2944 - 2944

Published: March 3, 2024

Mitochondrial dysfunction and metabolic reprogramming have been extensively studied in many disorders ranging from cardiovascular to neurodegenerative disease. Obesity has previously associated with mitochondrial fragmentation, dysregulated glycolysis, oxidative phosphorylation, as well increased reactive oxygen species production. Current treatments focus on reducing cellular stress restore homeostasis through the use of antioxidants or alterations dynamics. This review focuses role obesity particularly for those suffering asthma examines transfer mesenchymal stem cells function a potential therapy. targeted therapy healthy metabolism may provide unique approach alleviate dysregulation individuals this endotype.

Language: Английский

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Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases

npj Metabolic Health and Disease, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 3, 2025

Language: Английский

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Micronutrients/miRs/ATP networking in mitochondria: Clinical intervention with ferroptosis, cuproptosis, and calcium burden

Mitochondrion, Journal Year: 2023, Volume and Issue: 71, P. 1 - 16

Published: May 11, 2023

Language: Английский

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Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: from regulatory mechanism to targeted therapeutic strategy

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Oct. 13, 2023

Abstract Hypoxic-ischemic injury is a common pathological dysfunction in clinical settings. Mitochondria are sensitive organelles that readily damaged following ischemia and hypoxia. Dynamin-related protein 1 (Drp1) regulates mitochondrial quality cellular functions via its oligomeric changes multiple modifications, which plays role mediating the induction of organ damage during hypoxic-ischemic injury. However, there active controversy gaps knowledge regarding modification, interaction, Drp1, both hinder promote development Drp1 as novel therapeutic target. Here, we summarize recent findings on changes, modification types, interactions various diseases, well Drp1-mediated regulation cell Additionally, potential translation prospects for targeting discussed. This review provides new ideas targets proactive interventions induced by diseases.

Language: Английский

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Functionalized SWCNTs@Ag–TiO₂ nanocomposites induce ROS-mediated apoptosis and autophagy in liver cancer cells

Nanotechnology Reviews, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 1, 2023

Abstract Hybrid nanomaterials with unique physiochemical properties have received a lot of attention, making them attractive for application in different fields like cancer treatment. This study was designed to investigate the combined effects single-walled carbon nanotubes (SWCNTs) hybridized silver titanium dioxide composite (SWCNTs@Ag–TiO 2 ). Transmission electron microscopy and field emission scanning images demonstrated accumulation SWCNTs Ag–TiO due an increased main grain size functionalization 40 nm. The D G bands @Ag–TiO shifted 1,366 1,534 cm −1 , respectively. SWCNTs@Ag-TiO were assessed their cytotoxicity autophagy induction liver cells (Hep-G2) using lactate dehydrogenase assay, MTT flow cytometry methods. results showed that SWCNTs@Ag–TiO exhibited strong anti-cancer activity vitro against Hep-G2 by inducing apoptosis via controlling AKT JNK mitogen-activated protein kinase pathways. show coated silver/titanium ) reduce cells’ viability proliferation. It shown excessive amount reactive oxygen species crucial mediator both cell death caused . Based on these findings, it appears potential be developed as nanotherapeutics treatment cells.

Language: Английский

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Skeletal muscle atrophy after sciatic nerve damage: Mechanistic insights

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 970, P. 176506 - 176506

Published: March 15, 2024

Language: Английский

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Induction of mitochondrial toxicity by non-steroidal anti-inflammatory drugs (NSAIDs): The ultimate trade-off governing the therapeutic merits and demerits of these wonder drugs

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116283 - 116283

Published: May 14, 2024

Language: Английский

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The Complex Interplay between Toxic Hallmark Proteins, Calmodulin-Binding Proteins, Ion Channels, and Receptors Involved in Calcium Dyshomeostasis in Neurodegeneration

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 173 - 173

Published: Jan. 31, 2024

Calcium dyshomeostasis is an early critical event in neurodegeneration as exemplified by Alzheimer’s (AD), Huntington’s (HD) and Parkinson’s (PD) diseases. Neuronal calcium homeostasis maintained a diversity of ion channels, buffers, calcium-binding protein effectors, intracellular storage the endoplasmic reticulum, mitochondria, lysosomes. The function these components compartments impacted toxic hallmark proteins AD (amyloid beta Tau), HD (huntingtin) PD (alpha-synuclein) well interactions with downstream proteins, especially calmodulin. Each beta, Tau, huntingtin, alpha-synuclein) binds to Multiple channels receptors involved dysregulation also bind are regulated primary goal this review show complexity how they can impact research search for therapies. A secondary suggest that therapeutic targets from may offer greater opportunities success.

Language: Английский

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Deoxynivalenol leads to endoplasmic reticulum stress-mediated apoptosis via the IRE1/JNK/CHOP pathways in porcine embryos

Food and Chemical Toxicology, Journal Year: 2024, Volume and Issue: 188, P. 114633 - 114633

Published: April 10, 2024

Language: Английский

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