Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 17, 2022

Free radicals are formed as a part of normal metabolic activities but neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining redox balance. This balance is disrupted certain neuropathophysiological conditions, causing oxidative stress, which implicated several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression also caused excessive production free radicals. Highly reactive radicals, mainly oxygen species (ROS) and nitrogen (RNS), damage cell membrane, proteins, DNA, triggers self-propagating inflammatory cascade degenerative events. Dysfunctional mitochondria under stress conditions considered key mediator neurodegeneration. Exogenous delivery holds promise to alleviate regain In this regard, natural synthetic have been evaluated. Despite promising results preclinical studies, clinical translation therapy treat diseases remains elusive. The issues could be their low bioavailability, instability, limited transport target tissue, and/or poor antioxidant capacity, requiring repeated high dosing, cannot administered humans because dose-limiting toxicity. Our laboratory investigating nanoparticle-mediated enzymes address some above issues. Apart from being endogenous, main advantage catalytic mechanism action; hence, they significantly more effective at lower doses detoxifying deleterious effects than nonenzymatic antioxidants. review provides comprehensive analysis potential therapy, challenges translation, role nanoparticles/drug systems play addressing these challenges.

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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Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 834 - 834

Published: March 29, 2023

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It a ubiquitous molecule produced in organs, but its synthesis predominantly liver, tissue charge of storing and distributing it. GSH involved detoxification free radicals, peroxides xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, an important regulator cell homeostasis, since it participates signaling redox, regulation degradation proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, proliferation, DNA RNA synthesis, etc. transport vital step cellular homeostasis supported by liver through providing extrahepatic organs (such as kidney, lung, intestine, brain, among others) with said antioxidant. The wide range functions within which shows that glutathione’s role goes beyond being simple antioxidant agent; therefore, importance this tripeptide needs to be reassessed broader metabolic perspective.

Language: Английский

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Neuroprotective Effects of Olive Oil: A Comprehensive Review of Antioxidant Properties

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 762 - 762

Published: June 24, 2024

Neurodegenerative diseases are a significant challenge to global healthcare, and oxidative stress plays crucial role in their development. This paper presents comprehensive analysis of the neuroprotective potential olive oil, with primary focus on its antioxidant properties. The chemical composition including key antioxidants, such as oleuropein, hydroxytyrosol, oleocanthal, is systematically examined. mechanisms by which these compounds provide neuroprotection, counteracting damage modulating pathways, explored. efficacy oil evaluated synthesizing findings from various sources, vitro studies, animal models, clinical trials. integration into dietary patterns, particularly Mediterranean diet, broader implications neurodegenerative disease prevention also discussed. challenges translating preclinical applications acknowledged future research directions proposed better understand mitigating risk conditions. review highlights not only component, but promising candidate preventive neurology, advocating for further investigation context diseases.

Language: Английский

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Oxidative Stress as a Potential Mechanism Underlying Membrane Hyperexcitability in Neurodegenerative Diseases

Antioxidants, Journal Year: 2022, Volume and Issue: 11(8), P. 1511 - 1511

Published: Aug. 2, 2022

Neurodegenerative diseases are characterized by gradually progressive, selective loss of anatomically or physiologically related neuronal systems that produce brain damage from which there is no recovery. Despite the differences in clinical manifestations and vulnerability, pathological processes appear to be similar, suggesting common neurodegenerative pathways. It well known oxidative stress production reactive oxygen radicals plays a key role cell damage. has been proposed this stress, among other mechanisms, could contribute degeneration might one factors triggering development these pathologies. Another feature most neuron hyperexcitability, an aberrant electrical activity. This review, focusing mainly on primary motor cortex pyramidal neurons, critically evaluates idea inflammation may involved neurodegeneration via their capacity increase membrane excitability.

Language: Английский

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Therapeutic targeting ofALSpathways: Refocusing an incomplete picture

Annals of Clinical and Translational Neurology, Journal Year: 2023, Volume and Issue: 10(11), P. 1948 - 1971

Published: Aug. 28, 2023

Abstract Numerous potential amyotrophic lateral sclerosis (ALS)‐relevant pathways have been hypothesized and studied preclinically, with subsequent translation to clinical trial. However, few successes observed only modest effects. Along an improved but incomplete understanding of ALS as a neurodegenerative disease is the evolution more sophisticated diverse in vitro vivo preclinical modeling platforms, well trial designs. We highlight proposed pathological that major therapeutic targets for investigational compounds. It likely failures so many these compounds may not occurred because lack efficacy rather would help define appropriate pathway, failure establish target engagement. These challenges are compounded by shortcomings design, including biomarkers could predict success studies underpowered. Although research investments provided abundant insights into new ALS‐relevant pathways, most yet developed fully result study. In this review, we detail some important, well‐established therapeutics targeting them, design. With translational efforts over last three decades investigation, propose scientists clinicians choose revisit reviewed here eye toward improving modeling, biomarker development, investment

Language: Английский

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Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

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Biomarkers in Human Peripheral Blood Mononuclear Cells: The State of the Art in Amyotrophic Lateral Sclerosis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2580 - 2580

Published: Feb. 25, 2022

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the progressive loss of lower motor neurons, weakness and muscle atrophy. ALS lacks an effective cure diagnosis often made exclusion. Thus, it imperative to search for biomarkers. Biomarkers can help in understanding pathomechanisms, identification targets treatment development therapies. Peripheral blood mononuclear cells (PBMCs) represent valid source biomarkers compared cerebrospinal fluid, as they are simple collect, plasma, because possibility detecting expressed proteins. They reliable model patients’ stratification. This review provides overview on PBMCs potential ALS. We focused altered RNA metabolism (coding/non-coding RNA), including processing, mRNA stabilization, transport translation regulation. addressed protein abnormalities (aggregation, misfolding modifications); specifically, we highlighted that SOD1 appears be most characterizing Finally, emphasized correlation between biological parameters disease phenotypes, regards prognosis, severity clinical features. In conclusion, even though further studies needed standardize use tool biomarker investigation, promising approach research.

Language: Английский

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High-Fat Diet—Shared Environmental Risk Factor for Amyotrophic Lateral Sclerosis and Multiple Sclerosis

Sclerosis, Journal Year: 2025, Volume and Issue: 3(1), P. 1 - 1

Published: Jan. 12, 2025

Background: Amyotrophic lateral sclerosis (ALS) and multiple (MS) are, in essence, neurodegenerative disorders with significant individual, social, economic burdens worldwide. Despite having different clinical onset evolution, the two diseases share common risk factors underlying pathophysiological mechanisms. Environmental are particularly interesting, considering available effective counter strategies. High-fat diets remain a element that negatively impacts evolution of several disorders, including ALS MS. Focusing on changeable disease-related aspects is increasingly appealing context lack an treatment. Methods: This review aims to offer updated overview influence high-fat modulating progression MS, based search three relevant online databases. Results: In first part, shared mechanisms MS shown, differences between highlighted. Subsequently, most research this topic conducted animal models humans presented, bringing additional proof critical role neurodegeneration. Finally, current knowledge, authors potential therapeutic approaches future directions better control nutrition patients, hoping increase survival quality life. Conclusions: impact

Language: Английский

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Stress-related neurodegenerative diseases: Molecular mechanisms implicated in neurodegeneration and therapeutic strategies

Progress in brain research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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