New Insights on Dimethylaminoethanol (DMAE) Features as a Free Radical Scavenger

Malanga, Gabriela; Aguiar, María Belén; Martinez, Hugo D.; Puntarulo, Susana

doi:10.2174/187231212800229282

Cited by 20 publications

(7 citation statements)

References 35 publications

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“…This drug, which readily crosses the blood-brain barrier, has been reported to inhibit enzymes involved in PC biosynthesis [ 36 , 37 ], increase acetylcholine, scavenges radicals [ 38 ], and ameliorate rotenone-induced motor dysfunction in rodents [ 34 , 35 ]. MFX rapidly hydrolyzes into 4-chlorophenoxyacetic acid and dimethylethanolamine (DMAE) at neutral pH, and DMAE is considered to be the active product because of its ability to scavenge hydroxyl radicals [ 39 ]. DMAE can also couple with diacylglycerol to yield phosphatidyl-DMAE, which incorporates into membranes and scavenges radicals [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

Wang

Zhang

et al. 2016

PLoS ONE

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We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson’s disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo. In S. cerevisiae, the co-occurrence of low PE and α-syn in psd1Δ cells triggers mitochondrial defects, stress in the endoplasmic reticulum, misprocessing of glycosylphosphatidylinositol-anchored proteins, and a 3-fold increase in the level of α-syn. The goal of this study was to identify drugs that rescue this phenotype. We screened the Prestwick library of 1121 Food and Drug Administration-approved drugs using psd1Δ + α-syn cells and identified cyclosporin A, meclofenoxate hydrochloride, and sulfaphenazole as putative protective compounds. The protective activity of these drugs was corroborated using C. elegans in which α-syn is expressed specifically in the dopaminergic neurons, with psd-1 depleted by RNAi. Worm populations were examined for dopaminergic neuron survival following psd-1 knockdown. Exposure to cyclosporine, meclofenoxate, and sulfaphenazole significantly enhanced survival at day 7 in α-syn-expressing worm populations whereby 50–55% of the populations displayed normal neurons, compared to only 10–15% of untreated animals. We also found that all three drugs rescued worms expressing α-syn in dopaminergic neurons that were deficient in the phospholipid cardiolipin following cardiolipin synthase (crls-1) depletion by RNAi. We discuss how these drugs might block α-syn pathology in dopaminergic neurons.

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Section: Discussionmentioning

confidence: 99%

Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

Wang

Zhang

et al. 2016

PLoS ONE

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“…These results suggest that anti-oxidant effects could also play a role in DMAE suppression of Jlp1p inhibition. Previous studies of such effects for DMAE have been limited to much higher concentrations (Gabriela Malanga et al, 2012).…”

Section: Ros Assaysmentioning

confidence: 99%

A chemical screen for suppressors of dioxygenase inhibition in a yeast model of familial paraganglioma

Beimers

Braun

Schwinefus

et al. 2021

Preprint

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A fascinating class of familial paraganglioma (PGL) neuroendocrine tumors is driven by loss of the tricarboxylic acid (TCA) cycle enzyme succinate dehydrogenase (SDH) resulting in succinate accumulation as an oncometabolite, and other metabolic derangements. Here we exploit a S. cerevisiae yeast model of SDH loss where accumulating succinate, and possibly reactive oxygen species, poison a dioxygenase enzyme required for sulfur scavenging. Using this model we performed a chemical suppression screen for compounds that relieve dioxygenase inhibition. After testing 1280 pharmaceutically-active compounds we identified meclofenoxate HCL, and its hydrolysis product, dimethylaminoethanol (DMAE), as suppressors of dioxygenase intoxication in SDH-loss cells. We show that DMAE acts to alter metabolism so as to normalize the succinate:2-ketoglutarate ratio, improving dioxygenase function. This work raises the possibility that oncometabolite effects might be therapeutically suppressed by drugs that rewire metabolism to reduce the flux of carbon into pathological metabolic pathways.

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“…In animal experiments, ACh is used as a vasodilator for spasms of retinal arteries. In addition, DMAE has an antioxidant effect, since it is an inhibitor of free radicals (Malanga et al 2012).…”

Section: Introductionmentioning

confidence: 99%

A comparative evaluation of the efficacy of dimethylaminoethanol derivative 7–16, C7070 and picamilon in correction of experimental hypertensive neuroretinopathy

Peresypkina¹

2018

RRP

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Introduction. The efficacy of dimethylaminoethanol (DMAE) derivative 7–16, substance C7070 in comparison with picamylon in hypertensive neuroretinopathy model in white laboratory rats was evaluated. Materials and methods. For measuring the blood pressure, a system of noninvasive blood pressure measurement in small animals NIBP200 was used. Ophthalmoscopy was performed by using Bx a Neitz ophthalmoscope (Japan) and Osher MaxField 78D lens, OI-78M model. Electroretinography (ERG) was recorded in response to a single stimulation. Biopotentials were presented graphically on the screen with the help of BIOPAC SYSTEMS MP-150 with ACQKNOWLEDGE 4.2 software (USA). To assess a degree of a functional retinal disorder, the b/a coefficient was used. Results and discussion. The most pronounced protective effect on the model of hypertensive neuroretinopathy is demonstrated by C7070, which is expressed in the notable approximation to the normal eye fundus image and reaching the target values of the b/a coefficient. In the group with correction by DMAE derivative 7–16, a protective effect is observed, which exceeds picamilon, which is expressed in the elimination of soft and solid exudates, vein and venule plethora, vascular tortuosity, arterial spasm, Salus-Gunn I symptom, hemorrhages; the b/a increases significantly by 26% compared to the group without correction (p < 0.05). Conclusion. The eye fundus image and functional state of the retina are completely restored when correcting experimental hypertensive neuroretinopathy with C7070 in a dose of 50 mg/kg to laboratory rats and partially restored when correcting with DMAE derivative 7–16 in a dose of 25 mg/kg, which in both cases exceeds the protective effect of the reference drug picamilon on the model of hypertensive neuroretinopathy.

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New Insights on Dimethylaminoethanol (DMAE) Features as a Free Radical Scavenger

Cited by 20 publications

References 35 publications

Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

A chemical screen for suppressors of dioxygenase inhibition in a yeast model of familial paraganglioma

A comparative evaluation of the efficacy of dimethylaminoethanol derivative 7–16, C7070 and picamilon in correction of experimental hypertensive neuroretinopathy

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