Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy

The Neuroscientist, Год журнала: 2023, Номер 30(4), С. 440 - 457

Опубликована: Янв. 3, 2023

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in brain, which leads to loss neurons. Under microscope, function mitochondria uniquely primed play a pivotal role neuronal cell survival, energy metabolism, death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, defective mitophagy neurons are early indicators AD. This review article summarizes latest development AD: 1) mechanism pathways, 2) importance functions, 3) metabolic pathways 4) link between dysfunction mechanisms AD, 5) potential mitochondrial-targeted therapeutics interventions treat patients with

Язык: Английский

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Cardiac macrophages and emerging roles for their metabolism after myocardial infarction

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(18)

Опубликована: Сен. 14, 2023

Interest in cardioimmunology has reached new heights as the experimental cardiology field works to tap unrealized potential of immunotherapy for clinical care. Within this space is cardiac macrophage, a key modulator function health and disease. After myocardial infarction, myeloid macrophages both protect harm heart. To varying degrees, such outcomes are ontogeny heterogeneity, well functional cellular plasticity. Diversity further shaped by extracellular milieu, which fluctuates considerably after coronary occlusion. Ischemic limitation nutrients constrains metabolic immune cells, accumulating evidence supports paradigm whereby macrophage metabolism coupled divergent inflammatory consequences, although heart just emerging. Herein we examine heterogeneous response following ischemic injury, with focus on integrating putative contributions immunometabolism implications therapeutically relevant injury versus repair.

Язык: Английский

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Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Beyond the observed alterations in cellular structure and mitochondria, mechanisms linking rare genetic mutations to development of heart failure patients affected by desmin remain unclear due part, lack relevant human cardiomyocyte models.

Язык: Английский

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Mitochondrial Dysfunction as a Factor of Energy Metabolism Disorders in Type 2 Diabetes Mellitus

Frontiers in Bioscience-Scholar, Год журнала: 2024, Номер 16(1), С. 5 - 5

Опубликована: Март 8, 2024

The pathogenesis of type 2 diabetes mellitus (T2DM) is based on the development insulin resistance, which a disruption to ability tissues bind insulin, leading general metabolic disorder. Mitochondria are main participants in cellular energy metabolism, meaning their dysfunction associated with resistance T2DM. Mitochondrial function affected by various tissues, including skeletal muscle and liver, greatly influence glucose homeostasis throughout body. This review studies mitochondrial T2DM its impact disease progression. In addition, it considers causes underlying T2DM, mutations genome, DNA methylation, other epigenetic influences, as well impaired membrane potential. New therapeutic strategies for that have been developed target mitochondria will also be presented.

Язык: Английский

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From spreading depolarization to blood–brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy

Nature Reviews Neurology, Год журнала: 2024, Номер 20(7), С. 408 - 425

Опубликована: Июнь 17, 2024

Язык: Английский

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Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 364 - 364

Опубликована: Янв. 3, 2025

This review describes our current understanding of the role mitochondria in repurposing anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, obesity. Metformin, most prominent these diabetes drugs, has been called “Drug Miracles Wonders,” as trials have found it to be beneficial human patients suffering from maladies. To promote viral replication all infected cells, SARS-CoV-2 stimulates liver cells produce glucose export into blood stream, which can cause COVID patients, reduces levels blood, was shown cut incidence rate half recovering SARS-CoV-2. Metformin leads phosphorylation AMP-activated protein kinase AMPK, accelerates import via transporter GLUT4 switches starvation mode, counteracting virus. Diabetes also stimulate unfolded response thus mitophagy, is healthy aging health. were mimic exercise help reduce body weight.

Язык: Английский

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Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

Stem Cells, Год журнала: 2021, Номер 39(10), С. 1289 - 1297

Опубликована: Июнь 5, 2021

Abstract Mitochondria are organelles with recognized key roles in cellular homeostasis, including bioenergetics, redox, calcium signaling, and cell death. essential for neuronal function, given the high energy demands of human brain. Consequently, mitochondrial diseases affecting oxidative phosphorylation (OXPHOS) commonly exhibit neurological impairment. Emerging evidence suggests that mitochondria important not only mature postmitotic neurons but also regulation neural progenitor cells (NPCs) during process neurogenesis. These recent findings put as central regulator fate decisions brain development. OXPHOS mutations may disrupt function NPCs thereby impair metabolic programming required commitment. Promoting could therefore represent a novel interventional approach against incurable diseases.

Язык: Английский

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Mitochondrial Function and Parkinson’s Disease: From the Perspective of the Electron Transport Chain

Frontiers in Molecular Neuroscience, Год журнала: 2021, Номер 14

Опубликована: Дек. 9, 2021

Parkinson’s disease (PD) is known as a mitochondrial disease. Some even regarded it specifically disorder of the complex I electron transport chain (ETC). The ETC fundamental for energy production which essential neuronal health. In past two decades, more than 20 PD-associated genes have been identified. are directly involved in functions, such PRKN, PINK1 , and DJ-1 . While other PD-associate genes, LRRK2 SNCA GBA1 regulate lysosomal lipid metabolism, or protein aggregation, some shown to indirectly affect chain. recent identification CHCHD2 UQCRC1 that critical functions IV III, respectively, provide direct evidence PD just disorder. Like preventing cytochrome c from release, proteins beyond oxidative phosphorylation might also contribute pathogenesis PD.

Язык: Английский

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Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs

Molecules, Год журнала: 2022, Номер 27(11), С. 3494 - 3494

Опубликована: Май 29, 2022

Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding proteins, non-protein-coding RNA. Despite the great variability of affected in most severe cases, a neuromuscular and neurodegenerative phenotype is observed, no specific therapy exists for complete recovery disease. The used treatments are symptomatic based on administration antioxidant cocktails combined with antiepileptic/antipsychotic drugs supportive multiorgan involvement. Nevertheless, real utility cocktail patients by MDs still needs to be scientifically demonstrated. Unfortunately, clinical trials therapies using α-tocopherol, ascorbate, glutathione, riboflavin, niacin, acetyl-carnitine coenzyme Q have met limited success. Indeed, it would expected that employed antioxidants can only effective if they able target mechanism, i.e., involving central peripheral nervous system, responsible manifestations Noteworthily, very often phenotypes characterizing MD associated proteins whose function does not depend cofactors. Conversely, might determine suppression endogenous oxidants resulting deleterious effects cell viability and/or toxicity patients. In order avoid before administering therapy, useful ascertain blood serum levels cofactors administered It also worthwhile check localization should (less more directly) administered, estimating need predicting success proposed cofactor/antioxidant-based therapy.

Язык: Английский

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The Role of Mitochondrial DNA Mutations in Cardiovascular Diseases

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 952 - 952

Опубликована: Янв. 16, 2022

Cardiovascular diseases (CVD) are one of the leading causes morbidity and mortality worldwide. mtDNA (mitochondrial DNA) mutations known to participate in development progression some CVD. Moreover, specific types mitochondria-mediated CVD have been discovered, such as MIEH (maternally inherited essential hypertension) maternally CHD (coronary heart disease). Maternally mitochondrial is caused by certain mtDNA, which encode structural proteins tRNA. In this review, we focus on recently identified associated with artery disease hypertension). Additionally, new data suggest role Brugada syndrome ischemic stroke, before were considered only a result nuclear genes. discuss molecular mechanisms involvement disease.

Язык: Английский

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