Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy

Current Medicinal Chemistry, Год журнала: 2024, Номер 32(1), С. 23 - 54

Опубликована: Апрель 22, 2024

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted growing interest recent years. αLA is short- -chain sulfur-containing fatty occurring the mitochondria all kinds eukaryotic cells. Both oxidized disulfide and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent function. amount inside body gradually decreases with age resulting various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. primary objectives this study were analysis updated information on latest two-decade research regarding use an perspective. was collected PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, clinicaltrials.gov. Numerous silico, vitro, vivo, clinical studies revealed that shows protective role biological systems direct indirect reactive oxygen/nitrogen species quenching. demonstrated beneficial properties prevention treatment many age-related disorders neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, skin senescence. preventive case Alzheimer's Parkinson's diseases are particular interest. Further mechanistic highly recommended to evaluate wide spectrum therapeutic potential could optimize intake for alleviation related aging.

Язык: Английский

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Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462

Опубликована: Ноя. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Язык: Английский

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Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits

Antioxidants, Год журнала: 2024, Номер 13(10), С. 1228 - 1228

Опубликована: Окт. 12, 2024

Alpha-lipoic acid (ALA) is a bioactive molecule with significant health effects. The biological action of ALA has been ascribed to the characteristic antioxidant properties oxidized form and its reduced counterpart dihydrolipoic (DHLA) system. ALA/DHLA combination represents an ideal since it can quench radicals, able chelate metals, amphiphilic, no major adverse This unique system scavenge reactive oxygen species, exerting effect on tissue levels forms other antioxidants, including glutathione. For this reason, also known as "antioxidant antioxidants". review analyzes antioxidant, anti-inflammatory, neuroprotective effects discusses applications ameliorative tool for chronic diseases those associated oxidative stress. Results from in vitro vivo studies demonstrated that modulates various stress pathways suggesting application, alone or functional substances, useful support numerous conditions, which balance oxidant-antioxidant disrupted, such neurodegenerative disorders. Based several successful clinical studies, established oral supplements are clinically relieving complications diabetes disorders cardiovascular nerve discomforts be considered approach improving our health.

Язык: Английский

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Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(1)

Опубликована: Янв. 1, 2025

ABSTRACT Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions individuals. These characterized by pathological changes in various brain regions, specific genetic mutations associated with disease, deposits abnormal proteins, degeneration neurological cells. As neurodegenerative disorders vary their epidemiological characteristics vulnerability neurons, treatment these is usually aimed at slowing disease progression. The heterogeneity environmental factors involved process neurodegeneration makes current methods inadequate. However, existence common molecular mechanisms pathogenesis may allow development new targeted therapeutic strategies. Oxidative nitrosative stress damages membrane components accumulating ROS RNS disrupting redox balance. This results induction apoptosis, which important through oxidative stress. Studies conducted using postmortem human samples, animal models, cell cultures demonstrated stress, apoptosis crucial such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, Huntington's disease. excessive production reactive oxygen nitrogen species, elevated levels free radicals, heightened mitochondrial disturbances energy metabolism, oxidation nitrosylation cellular macromolecules recognized triggers neuronal death. Challenges managing treating require better understanding this field level. Therefore, review elaborates apoptosis.

Язык: Английский

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Chemoproteomic target deconvolution reveals Histone Deacetylases as targets of (R)-lipoic acid

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 15, 2023

Lipoic acid is an essential enzyme cofactor in central metabolic pathways. Due to its claimed antioxidant properties, racemic (R/S)-lipoic used as a food supplement but also investigated pharmaceutical over 180 clinical trials covering broad range of diseases. Moreover, approved drug for the treatment diabetic neuropathy. However, mechanism action remains elusive. Here, we performed chemoproteomics-aided target deconvolution lipoic and active close analog lipoamide. We find that histone deacetylases HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10 are molecular targets reduced form Importantly, only naturally occurring (R)-enantiomer inhibits HDACs at physiologically relevant concentrations leads hyperacetylation HDAC substrates. The inhibition by (R)-lipoic lipoamide explain why both compounds prevent stress granule formation cells may provide rationale many other phenotypic effects elicited acid.

Язык: Английский

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α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(40)

Опубликована: Сен. 26, 2023

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and required cell growth, metabolic fuel production, antioxidant defense. In vitro, LA binds copper (Cu) with high affinity as endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload human diseases. We tested this hypothesis 3T3-L1 preadipocytes inactivated transporter Atp7a; these cells accumulate show morphologic changes mitochondria impairment. Treatment corrected morphology Atp7a −/− similar to chelator bathocuproinedisulfonate (BCS) improved function; however, mechanisms BCS action were different. Unlike BCS, did not decrease intracellular but instead increased selenium levels that low cells. Proteome analysis confirmed distinct responses compounds identified upregulation selenoproteins major effect on preadipocytes. Upregulation was associated GSH:GSSG ratio cellular compartments, which lowered by elevated Cu, reversal protein oxidation. Thus, diminishes toxic effects improving redox environment. also are decreased tissues a Wilson disease animal model, especially liver, making attractive candidate supplemental treatment disease.

Язык: Английский

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Epilepsy: Mitochondrial connections to the ‘Sacred’ disease

Mitochondrion, Год журнала: 2023, Номер 72, С. 84 - 101

Опубликована: Авг. 13, 2023

Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms epilepsy makes diagnosis challenging. Diagnosis and monitoring childhood add to the need non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms epileptogenesis are not fully understood, evidence mitochondrial involvement is substantial. Seizures affect 35%-60% patients diagnosed with diseases. Mitochondrial dysfunction pathophysiological in various epilepsies, including those non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads altered neuronal bioenergetics, metabolism neurological complications, Iron-dependent lipid peroxidation initiates ferroptosis, a death pathway that aligns morphology found neurodegenerative diseases (NDDs). Studies mouse genetic models seizure phenotypes where function an essential selenoprotein (GPX4) targeted suggest roles ferroptosis epilepsy. GPX4 pivotal NDDs, selenium protects interneurons ferroptosis. Selenium central nervous system micronutrient trace element. Low serum concentrations other elements minerals, iron, noted diagnosing supplements alleviate intractable seizures children reduced GPX activity. Copper cuproptosis, like iron link NDDs. Connecting these mechanistic pathways selenoproteins provides new insights into treating seizures, pointing using medicines prodrugs lipoic acid treat potential alternative therapeutic approaches transcranial magnetic stimulation (transcranial), photobiomodulation vagus nerve stimulation.

Язык: Английский

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Recent developments in encapsulation of α-lipoic acid for enhanced bioavailability and stability

Quality Assurance and Safety of Crops & Foods, Год журнала: 2023, Номер 15(1), С. 123 - 138

Опубликована: Янв. 14, 2023

α-lipoic acid (LA) is a potent antioxidant available in various plant and animal sources. Of late, there high market demand for LA-based nutraceuticals, owing to enhanced occurrences of oxidative stress-based diseases. However, the effectiveness LA challenged with its low solubility, less stability, bioavailability. In addition, unpleasant taste limits applications food systems. this context, encapsulation techniques can modify chemical biological properties improve solubility stability aqueous medium, which turn helps development different innovative therapeutic products based on LA. Different such as inclusion complexes, spray drying, electrospraying, solid lipid nanoparticles (SLN), emulsification, liposomes have been explored This review focuses activities terms antioxidant, antidiabetic, anticancer, anti-inflammatory properties, scope enhance these evidenced through vitro vivo studies. Furthermore, article will help researchers industrialists select suitable method their requirement delivering achieve optimal potential.

Язык: Английский

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Update on Treating Painful Diabetic Peripheral Neuropathy: A Review of Current US Guidelines with a Focus on the Most Recently Approved Management Options

Journal of Pain Research, Год журнала: 2024, Номер Volume 17, С. 1005 - 1028

Опубликована: Март 1, 2024

Painful diabetic peripheral neuropathy (DPN) is a highly prevalent and disabling complication of diabetes that often misdiagnosed undertreated. The management painful DPN involves treating its underlying cause via lifestyle modifications intensive glucose control, targeting pathogenesis, providing symptomatic pain relief, thereby improving patient function health-related quality life. Four pharmacologic options are currently approved by the US Food Drug Administration (FDA) to treat DPN. These include three oral medications (duloxetine, pregabalin, tapentadol extended release) one topical agent (capsaicin 8% system). More recently, FDA several spinal cord stimulation (SCS) devices refractory Although not FDA-approved specifically DPN, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, gabapentinoids, sodium channel blockers common first-line in clinical practice. Other strategies may be used as part individualized comprehensive plans. This article provides an overview most recent guidelines for managing with focus on two recently treatment (SCS capsaicin system), well evidence using guideline-supported drugs devices. Also discussed unmet needs this population, potential future treatments including novel mechanisms action, electrical devices, nutraceuticals.

Язык: Английский

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Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review

Nutrients, Год журнала: 2023, Номер 15(16), С. 3634 - 3634

Опубликована: Авг. 18, 2023

Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating effects of oral-administered ALA versus a placebo DSPN determining optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) PubMed, Embase, Cochrane databases determine efficacy oral DSPN. The primary outcome total symptoms’ score (TSS), secondary outcomes were neurological disability (NDS), impaired (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, global satisfaction. A subgroup analysis (600, 1200, 1800 mg/day) also conducted. Ten RCTs (1242 patients) included. treatment produced favorable results TSS (a dose-related trend observed), NDS, satisfaction score. For VAS, VPT, NIS-LL, NCS did not produce results. had on sensory symptoms, it resulted dose-dependent response relative use prevent should be further researched.

Язык: Английский

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