Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

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Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson’s disease

Neuron, Journal Year: 2022, Volume and Issue: 110(15), P. 2422 - 2437.e9

Published: June 1, 2022

Language: Английский

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Mitochondrial dysfunction: A fatal blow in depression

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115652 - 115652

Published: Oct. 4, 2023

Mitochondria maintain the normal physiological function of nerve cells by producing sufficient cellular energy and performing crucial roles in maintaining metabolic balance through intracellular Ca2+ homeostasis, oxidative stress, axonal development. Depression is a prevalent psychiatric disorder with an unclear pathophysiology. Damage to hippocampal neurons key component plasticity regulation synapses plays critical role mechanism depression. There evidence suggesting that mitochondrial dysfunction associated synaptic impairment. The maintenance homeostasis includes quantitative quality control mitochondria. Mitochondrial biogenesis produces new healthy mitochondria, dynamics cooperates mitophagy remove damaged These processes population stability exert neuroprotective effects against early In contrast, observed various brain regions patients major depressive disorders. accumulation defective mitochondria accelerates dysfunction. addition, impaired aggravate alterations microenvironment, promoting neuroinflammation depletion, thereby exacerbating development This review summarizes influence underlying molecular pathways on pathogenesis Additionally, we discuss as potential therapeutic strategy for

Language: Английский

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Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13033 - 13033

Published: Aug. 22, 2023

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death neurons, leading to range neurological symptoms. Despite heterogeneity these conditions, common denominator is implication mitochondrial dysfunction in their pathogenesis. Mitochondria play crucial role creating biomolecules, providing energy through adenosine triphosphate (ATP) generated oxidative phosphorylation (OXPHOS), producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented losing membrane potential, they contribute diseases. In this review, we explore how mitochondria fuse undergo fission, especially context NDs. We discuss genetic protein mutations linked impact dynamics. also look at key regulatory proteins fusion (MFN1, MFN2, OPA1) fission (DRP1 FIS1), including post-translational modifications. Furthermore, highlight potential drugs that can influence By unpacking complex processes, aim direct research towards treatments improve life quality for people with challenging conditions.

Language: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

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Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases

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

Published: March 15, 2024

Mounting evidence progressively appreciates the vital interplay between immunity and metabolism in a wide array of immunometabolic chronic disorders, both autoimmune non-autoimmune mediated. The immune system regulates functioning cellular within organs like brain, pancreas and/or adipose tissue by sensing adapting to fluctuations microenvironment’s nutrients, thereby reshaping metabolic pathways that greatly impact pro- or anti-inflammatory immunophenotype. While it is agreed relies on an adequate nutritional status function properly, we are only just starting understand how supply single combined all them termed immunonutrients, can steer cells towards less inflamed, tolerogenic Polyphenols, class secondary metabolites abundant Mediterranean foods, pharmacologically active natural products with outstanding immunomodulatory actions. Upon binding range receptors highly expressed (e.g. AhR, RAR, RLR), they act through mitochondria-centered multi-modal approach. First , polyphenols activate nutrient via stress-response pathways, essential for responses. Second regulate mammalian target rapamycin (mTOR)/AMP-activated protein kinase (AMPK) balance well-tolerated caloric restriction mimetics. Third interfere assembly NLR family pyrin domain containing 3 (NLRP3) endoplasmic reticulum-mitochondria contact sites, inhibiting its activation while improving mitochondrial biogenesis autophagosome-lysosome fusion. Finally chromatin remodeling coordinates epigenetic reprogramming. This work moves beyond well-documented antioxidant properties polyphenols, offering new insights into multifaceted nature these compounds. It proposes mechanistical appraisal regulatory which modulate response, alleviating low-grade inflammation. Furthermore, draws parallels pharmacological interventions polyphenol-based immunonutrition their modes immunomodulation across spectrum socioeconomically impactful diseases such as Multiple Sclerosis, Diabetes (type 1 2) even Alzheimer’s disease. Lastly, discusses existing challenges thwart translation polyphenols-based immunonutritional long-term clinical studies. Overcoming limitations will undoubtedly pave way precision nutrition protocols provide personalized guidance tailored plans.

Language: Английский

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A human brain map of mitochondrial respiratory capacity and diversity

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

Published: March 26, 2025

Language: Английский

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Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 95, P. 101136 - 101136

Published: Nov. 16, 2022

Glaucoma is a leading cause of irreversible blindness worldwide and characterized by slow, progressive, multifactorial degeneration retinal ganglion cells (RGCs) their axons, resulting in vision loss. Despite its high prevalence individuals 60 years age older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) only proven treatable risk factor. However, lowering IOP insufficient for preventing disease progression. One significant interests pathogenesis understanding structural functional impairment mitochondria RGCs axons synapses. Glaucomatous such as elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, vascular dysregulation, potential inducers mitochondrial dysfunction glaucoma. Because oxidative phosphorylation stress-mediated associated with glaucomatous RGCs, underlying mechanisms relationship between alterations would be beneficial developing mitochondria-related neuroprotection synapses against neurodegeneration. Here, we review current studies focusing on dynamics-based therapeutic strategies protect

Language: Английский

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The Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2049 - 2049

Published: June 28, 2022

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and highly fatal neurodegenerative disease. Although the pathogenesis of ALS remains unclear, increasing evidence suggests that key contributing factor mitochondrial dysfunction. Mitochondria are organelles in eukaryotic cells responsible for bioenergy production, cellular metabolism, signal transduction, calcium homeostasis, immune responses stability their function plays crucial role neurons. A single disorder or defect can lead to pathological changes cells, such as an impaired buffer period, excessive generation free radicals, increased membrane permeability, oxidative stress (OS). Recent research has also shown these dysfunctions associated with believed be commonly involved This article reviews latest on dysfunction its impact progression ALS, specific attention potential novel therapeutic strategies targeting

Language: Английский

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Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Language: Английский

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