Role of lipoic acid in multiple sclerosis

Xie, Hongsheng; Yang, Xiaobin; Cao, Yuan; Long, Xipeng; Shang, Huifang; Jia, Zhiyun

doi:10.1111/cns.13793

Cited by 22 publications

(9 citation statements)

References 114 publications

(139 reference statements)

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“…Studies in a mouse model of multiple sclerosis indicate that ALA inhibits neuronal demyelination by reducing metalloproteinases activity. 110 MMP-2 promotes the passage of blood lymphocytes into the CNS; thus, its pharmacological blockade may have important clinical implications.…”

Section: Discussionmentioning

confidence: 99%

α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the β-Amyloid Accumulation

Maciejczyk

Żebrowska

Nesterowicz

et al. 2022

JIR

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Background Oxidative stress underlies metabolic diseases and cognitive impairment; thus, the use of antioxidants may improve brain function in insulin-resistant conditions. We are the first to evaluate the effects of α-lipoic acid (ALA) on redox homeostasis, sphingolipid metabolism, neuroinflammation, apoptosis, and β-amyloid accumulation in the cerebral cortex and hypothalamus of insulin-resistant rats. Methods The experiment was conducted on male cmdb/outbred Wistar rats fed a high-fat diet (HFD) for 10 weeks with intragastric administration of ALA (30 mg/kg body weight) for 4 weeks. Pro-oxidant and pro-inflammatory enzymes, oxidative stress, sphingolipid metabolism, neuroinflammation, apoptosis, and β-amyloid level were assessed in the hypothalamus and cerebral cortex using colorimetric, fluorimetric, ELISA, and HPLC methods. Statistical analysis was performed using three-way ANOVA followed by the Tukey HSD test. Results ALA normalizes body weight, food intake, glycemia, insulinemia, and systemic insulin sensitivity in HFD-fed rats. ALA treatment reduces nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidase activity, increases ferric-reducing antioxidant power (FRAP) and thiol levels in the hypothalamus of insulin-resistant rats. In addition, it decreases myeloperoxidase, glucuronidase, and metalloproteinase-2 activity and pro-inflammatory cytokines (IL-1β, IL-6) levels, while in the cerebral cortex ALA reduces β-amyloid accumulation. In both brain structures, ALA diminishes ceramide synthesis and caspase-3 activity. ALA improves systemic oxidative status and reduces insulin-resistant rats’ serum cytokines, chemokines, and growth factors. Conclusion ALA normalizes lipid and carbohydrate metabolism in insulin-resistant rats. At the brain level, ALA primarily affects hypothalamic metabolism. ALA improves redox homeostasis by decreasing the activity of pro-oxidant enzymes, enhancing total antioxidant potential, and reducing protein and lipid oxidative damage in the hypothalamus of HFD-fed rats. ALA also reduces hypothalamic inflammation and metalloproteinases activity, and cortical β-amyloid accumulation. In both brain structures, ALA diminishes ceramide synthesis and neuronal apoptosis. Although further study is needed, ALA may be a potential treatment for patients with cerebral complications of insulin resistance.

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Section: Discussionmentioning

confidence: 99%

α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the β-Amyloid Accumulation

Maciejczyk

Żebrowska

Nesterowicz

et al. 2022

JIR

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“…Lipoic acid has varied roles in the immune system, including inhibiting NFκB, keeping inflammatory cells from crossing the blood-brain barrier, and inhibiting LFA-2, ICAM1, VLA-4, VCAM-1, and MMP-9. It decreases levels of both TNF-alpha and IFN-gamma and neutralizes reactive oxygen species and NO [ 226 ]. It also activates the insulin receptor and activates AMPK, which is the critical regulator of AMP-activated protein kinase.…”

Section: Other Cofactorsmentioning

confidence: 99%

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

Indika

Frye²,

Rossignol³

et al. 2023

JPM

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Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use.

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“…This molecule has multiple biological functions, and so far, it is the bioactive compound that possesses the most robust evidence for efficacy in MS [ 133 ]. The in vitro and in vivo studies revealed that alpha-lipoic acid can protect neuron cells by inhibiting the expression of inflammatory mediators and by decreasing the immune cell infiltration in the CNS [ 134 ]. Furthermore, in clinical studies, the compound improved the patients’ walking performance, gait, and balance.…”

Section: Natural Compounds In Clinical Trials For Neurodegenerative D...mentioning

confidence: 99%

Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials

et al. 2023

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Neurodegenerative diseases are caused by the gradual loss of neurons’ function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds’ therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds’ safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease.

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Role of lipoic acid in multiple sclerosis

Cited by 22 publications

References 114 publications

α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the β-Amyloid Accumulation

α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the β-Amyloid Accumulation

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials

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