Lipoic Acid and Other Antioxidants as Therapies for Multiple Sclerosis

Waslo, Carin S.; Bourdette, Dennis; Gray, Nora E.; Wright, Kirsten M.; Spain, Rebecca

doi:10.1007/s11940-019-0566-1

Cited by 33 publications

(12 citation statements)

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“…Oxidative stress is implicated as one of the key factors in the pathogenesis of MS, given that evidence for oxidative stress is found in the experimental autoimmune encephalomyelitis, pathologic specimens, and autopsied tissues from MS patients, and antioxidant therapy is reported to be a promising approach to treat MS 35 . Activated macrophages and microglia and mitochondrial dysfunction are the main sources for oxidative stress in MS lesions 15 .…”

Section: Discussionmentioning

confidence: 99%

“…Differing from Gd enhancement of an MS lesion, which represents the disruption of the blood–brain barrier, elevated ROS production and inflammation is reported to be present in active and slowly expanding MS lesions, but may be absent in inactive MS lesions 35,37 . Therefore, detection and visualization of ROS in vivo is essential for studying oxidative stress in MS pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

Shaghaghi

Chen

et al. 2020

Magnetic Resonance Imaging

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BackgroundCurrently available radiological methods do not completely capture the diversity of multiple sclerosis (MS) lesion subtypes. This lack of information hampers the understanding of disease progression and potential treatment stratification. For example, inflammation persists in some lesions after gadolinium (Gd) enhancement resolves. Novel metabolic and molecular imaging methods may improve the current assessments of MS pathophysiology.PurposeTo compare the in vivo proton exchange rate (kex) MRI with Gd‐enhanced MRI for characterizing MS lesions.Study TypeRetrospective.SubjectsSixteen consecutively diagnosed relapsing‐remitting multiple sclerosis (RRMS) patients.Field Strength/Sequence3.0T MRI with T2‐weighted imaging, postcontrast T1‐weighted imaging, and single‐slice chemical exchange saturation transfer imaging.AssessmentMS lesions in white matter were assessed for Gd enhancement and kex elevation compared to normal‐appearing white matter (NAWM).Statistical TestsStudent's t‐test was used for analyzing the difference of kex values between lesions and NAWM, with statistical significance set at 0.05.ResultsOf all 153 MS lesions, 78 (51%) lesions were Gd‐enhancing and 75 (49%) were Gd‐negative. Without exception, all 78 Gd‐enhancing lesions showed significantly elevated kex values compared to NAWM (924 ± 130 s–1 vs. 735 ± 61 s–1, P < 0.05). Of 75 Gd‐negative lesions, 18 lesions (24%) showed no kex elevation (762 ± 29 s–1 vs. 755 ± 28 s–1, P = 0.47) and 57 (76%) showed significant kex elevation (950 ± 124 s–1 vs. 759 ± 48 s–1, P < 0.05) compared to NAWM. MS lesions with kex elevation appeared nodular (118, 87.4%), ring‐like (15, 11.1%), or irregular‐shaped (2, 1.5%).Data ConclusionFor Gd‐enhancing lesions, kex MRI is highly consistent with Gd‐enhanced images by showing 100% of elevated kex. For all Gd‐negative lesions, the discrepancy on kex MRI may further differentiate active slowly expanding lesions or chronic inactive lesions, supporting kex as an imaging biomarker for tissue oxidative stress and inflammation.Level of Evidence 2Technical Efficacy Stage 3J. MAGN. RESON. IMAGING 2021;53:408–415.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

Shaghaghi

Chen

et al. 2020

Magnetic Resonance Imaging

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“…It has been proven that LA exhibits anti-tumor activities in several cancer models by impacting several hallmarks on most of the signaling pathways implicated in proliferation, invasion, migration, epithelial-mesenchymal transition, stemness and apoptosis [2]. Very recent pre-clinical and limited clinical trial evidence have suggested LA as a leading candidate in multiple sclerosis therapy [7]. This compound is able to regulate the immune system in either direct or indirect ways.…”

Section: Introductionmentioning

confidence: 99%

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma

Borowczyk

Olejarz

Chwatko

et al. 2020

IJMS

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α-Lipoic acid, glutathione, cysteine, and cysteinylglycine can be applied as therapeutic agents in civilization diseases such as diabetes mellitus, cardiovascular diseases, and cancers. On the other hand, a higher concentration of homocysteine can result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. Here, the first simplified HPLC-UV assay that enables simultaneous determination of α-lipoic acid and low-molecular-mass thiols in plasma, reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials is described. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearity in the detector responses for plasma samples were observed in ranges: 0.12–5.0 nmol mL−1 for α-lipoic acid; 2.0–20.0 nmol mL−1 for glutathione, cysteinylglycine, and homocysteine; and 40.0–400.0 for cysteine. The LODs for α-lipoic acid and low-molecular-mass thiols were 0.08 and 0.12 nmol mL−1, respectively, while LOQs were 0.12 and 0.16 nmol mL−1, respectively. The usefulness of the proposed method has been proven by its application to real samples.

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“…61,70,71,74,[77][78][79][80] Manifestations of OS are hallmark symptoms in neurological disease, including cognitive deficits. 52,54,65,76,79,[81][82][83][84][85][86][87][88] In concert with the above, a correlation was found between OS in the CNS and demyelination, which results in the loss of integrity and proper maintenance of oligodendrocytes and their myelin sheaths, the latter being crucial for cognitive performance and higher brain function. 57,[89][90][91] Thus, inclusion of strategies for enhancing mitochondrial biogenesis, function, and protection 68,80,[92][93][94][95][96] that may also rely on pathways epigenetically induced by diet [97][98][99][100][101][102][103][104][105][106][107][108] and/or exercise 99,100,…”

Section: Introductionmentioning

confidence: 76%

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Moos

Faller

Glavas

et al. 2020

BioResearch Open Access

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In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

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Lipoic Acid and Other Antioxidants as Therapies for Multiple Sclerosis

Cited by 33 publications

References 100 publications

In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

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Lipoic Acid and Other Antioxidants as Therapies for Multiple Sclerosis

Cited by 33 publications

References 100 publications

In Vivo Proton Exchange Rate (kex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

In Vivo Proton Exchange Rate (kex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

Contact Info

Product

Resources

About

In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients

In Vivo Proton Exchange Rate (k_ex) MRI for the Characterization of Multiple Sclerosis Lesions in Patients