Mitochondria-Targeted Antioxidants, an Innovative Class of Antioxidant Compounds for Neurodegenerative Diseases: Perspectives and Limitations

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3739 - 3739

Опубликована: Фев. 13, 2023

Neurodegenerative diseases comprise a wide spectrum of pathologies characterized by progressive loss neuronal functions and structures. Despite having different genetic backgrounds etiology, in recent years, many studies have highlighted point convergence the mechanisms leading to neurodegeneration: mitochondrial dysfunction oxidative stress been observed pathologies, their detrimental effects on neurons contribute exacerbation pathological phenotype at various degrees. In this context, increasing relevance has acquired antioxidant therapies, with purpose restoring order revert damage. However, conventional antioxidants were not able specifically accumulate diseased mitochondria, often eliciting harmful whole body. last decades, novel, precise, mitochondria-targeted (MTA) compounds developed studied, both vitro vivo, address need counter mitochondria restore energy supply membrane potentials neurons. review, we focus activity therapeutic perspectives MitoQ, SkQ1, MitoVitE MitoTEMPO, most studied belonging class MTA conjugated lipophilic cations, reach compartment.

Язык: Английский

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Exercise therapy to prevent and treat Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Авг. 4, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition amyloid beta (Aβ) phosphorylated tau, age, mitochondrial defects, neuroinflammation, decreased synaptic connections, nerve growth factors (NGF). While animals moderate-intensity exercise restores hippocampal amygdala through levels p-AKT, p-TrkB, p-PKC Aβ, tau phosphorylation, precursor proteins (APP) AD. Aerobic (with an intensity 50–75% VO2 max) prevents volume reduction, spatial learning reduction increasing flexibility. Exercise training induces binding brain-derived neurotrophic factor (BDNF) to TrkB NGF TrkA induce cell survival neuronal plasticity. After aerobic high-intensity interval training, increase VEGF, angiopoietin 1 2, NO, tPA, HCAR1 cerebral vessels blood flow angiogenesis cerebellum, motor cortex, striatum, hippocampus. In hippocampus, decreases fragmentation, DRP1, FIS1, improving OPA1, MFN1, MFN2, morphology. humans, acute as anti-inflammatory condition IL-6 such IL-1RA IL-10. Moderate-intensity also inhibits inflammatory markers IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, NF-κB. significantly increases plasma BDNF, factor, plasticity, activity, memory, exploratory behavior subjects. Irisin myokine released from skeletal muscle during protects hippocampus by suppressing Aβ accumulation promoting proliferation STAT3 signaling. Therefore, combined strength balance coordination social activities seems provide important benefits for people

Язык: Английский

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Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00525 - e00525

Опубликована: Янв. 1, 2025

Язык: Английский

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Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer’s Disease

Antioxidants, Год журнала: 2022, Номер 11(4), С. 692 - 692

Опубликована: Март 31, 2022

Alzheimer’s disease (AD) is a devastating progressive neurodegenerative characterized by neuronal dysfunction, and decreased memory cognitive function. Iron critical for activity, neurotransmitter biosynthesis, energy homeostasis. accumulation occurs in AD results dysfunction through activation of multifactorial mechanisms. Mitochondria generate iron key co-factor required for: (1) ATP production the electron transport chain, (2) heme protein biosynthesis (3) iron-sulfur cluster formation. Disruptions homeostasis result mitochondrial energetic failure. Ferroptosis, non-apoptotic iron-dependent form cell death mediated uncontrolled reactive oxygen species lipid peroxidation, associated with other diseases. pathogenesis complex multiple diverse interacting players including Aβ-plaque formation, phosphorylated tau, redox stress. Unfortunately, clinical trials based on targeting these canonical hallmarks have been largely unsuccessful. Here, we review evidence linking dysregulation to potential ferroptosis as therapeutic intervention AD.

Язык: Английский

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Mitochondrial disorders leading to Alzheimer’s disease—perspectives of diagnosis and treatment

GeroScience, Год журнала: 2024, Номер 46(3), С. 2977 - 2988

Опубликована: Март 8, 2024

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia globally. The pathogenesis AD remains still unclear. three main features are extracellular deposits amyloid beta (Aβ) plaque, accumulation abnormal formation hyper-phosphorylated tau protein, neuronal loss. Mitochondrial impairment plays an important role in AD. There problems with decreased activity multiple complexes, disturbed mitochondrial fusion, fission or reactive oxygen species (ROS). Moreover, transport impaired Mouse models many research show disruptions anterograde retrograde transport. Both transportation network have huge impact on synapse loss and, as result, cognitive impairment. One very serious also disruption insulin signaling which impairs Aβ removal. Discovering precise mechanisms leading to enables us find new treatment possibilities. Recent studies indicate positive influence metformin antioxidants such MitoQ, SS-31, SkQ, MitoApo, MitoTEMPO, MitoVitE functioning hence prevent decline. Impairments may be treated division inhibitor-1 ceramide. Graphical (Graphic content via Canva Pro)

Язык: Английский

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Mitochondrial DNA and Inflammation in Alzheimer’s Disease

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(11), С. 8586 - 8606

Опубликована: Окт. 25, 2023

Mitochondrial dysfunction and neuroinflammation are implicated in the pathogenesis of most neurodegenerative diseases, such as Alzheimer’s disease (AD). In fact, although a growing number studies show crosstalk between these two processes, there remain numerous gaps our knowledge mechanisms involved, which requires further clarification. On one hand, mitochondrial may lead to release damage-associated molecular patterns (mtDAMPs) recognized by microglial immune receptors contribute progression. other inflammatory molecules released glial cells can influence regulate function. A deeper understanding help identify biomarkers targets useful for treatment diseases. This review works published recent years is focused on description contribution neurodegeneration, with particular attention DNA (mtDNA) AD.

Язык: Английский

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Mitochondrial mechanisms in Alzheimer’s disease: Quest for therapeutics

Drug Discovery Today, Год журнала: 2023, Номер 28(5), С. 103547 - 103547

Опубликована: Март 5, 2023

Язык: Английский

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The Neuroprotective Flavonoids Sterubin and Fisetin Maintain Mitochondrial Health under Oxytotic/Ferroptotic Stress and Improve Bioenergetic Efficiency in HT22 Neuronal Cells

Antioxidants, Год журнала: 2024, Номер 13(4), С. 460 - 460

Опубликована: Апрель 13, 2024

The global increase in the aging population has led to a rise many age-related diseases with continuing unmet therapeutic needs. Research into molecular mechanisms underlying both and neurodegeneration identified promising targets, such as oxytosis/ferroptosis cell death pathway, which mitochondrial dysfunction plays critical role. This study focused on sterubin fisetin, two flavonoids from natural pharmacopeia previously strong inhibitors of pathway. Here, we investigated effects compounds physiology HT22 hippocampal nerve cells under oxytotic/ferroptotic stress. We show that can restore homeostasis at level redox regulation, calcium uptake, biogenesis, fusion/fission dynamics, modulation respiration, leading enhancement bioenergetic efficiency. However, mitochondria are not required for neuroprotective highlighting their diverse homeostatic impacts. Sterubin thus, provide opportunities expand drug development strategies anti-oxytotic/ferroptotic agents offer new perspectives intricate interplay between function, cellular stress, pathophysiology neurodegenerative disorders.

Язык: Английский

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Altered metabolism and DAM-signatures in female brains and microglia with aging

Brain Research, Год журнала: 2024, Номер 1829, С. 148772 - 148772

Опубликована: Янв. 18, 2024

Язык: Английский

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Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 11, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss. Despite advances in understanding the pathophysiological mechanisms of AD, effective treatments remain scarce. Lithium salts, recognized as mood stabilizers bipolar disorder, have been extensively studied for their neuroprotective effects. Several studies indicate that lithium may be disease-modifying agent treatment AD. Lithium’s properties AD acting on multiple neuropathological targets, such reducing amyloid deposition tau phosphorylation, enhancing autophagy, neurogenesis, synaptic plasticity, regulating cholinergic glucose metabolism, inhibiting neuroinflammation, oxidative stress, apoptosis, while preserving mitochondrial function. Clinical trials demonstrated therapy can improve function patients with In particular, meta-analyses shown more safer than recently FDA-approved aducanumab improving The affordability therapeutic efficacy prompted reassessment its use. However, use lead to potential side effects safety issues, which limit clinical application. Currently, several new formulations are undergoing efficacy. This review focuses lithium’s mechanism action treating highlighting latest preclinical trials. It also explores coping strategies, offering strategy

Язык: Английский

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