Carnitine: transport and physiological functions in the brain

Nałęcz, Katarzyna A.; Miecz, Dorota; Bérézowski, Vincent; Cecchelli, Roméo

doi:10.1016/j.mam.2004.06.001

Cited by 95 publications

(66 citation statements)

References 124 publications

(116 reference statements)

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“…It has poor pharmacokinetic properties (short half-life and first-pass hepatic clearance) and multigram doses are needed to achieve therapeutic concentrations in vivo Moos et al, 2016]. However, when butyrate and other SCFAs, including lipoic acid, present as acylcarnitine esters [Knoop, 1904;Bieber et al, 1982;Bieber, 1988;Nałezcz et al, 2004;Houten and Wanders, 2010], the body's natural carnitine-acylcarnitine transport machinery actively delivers the ester into cells, an effect that substantially increases the bioavailability of the corresponding acyl-CoA [Chenault et al, 1988;Billhardt et al, 1989;Srinivas et al, 2007;Gong et al, 2008;Piermatti et al, 2008;Rosca et al, 2009;Steliou et al, 2009Steliou et al, , 2012Parameshwaran et al, 2010Parameshwaran et al, , 2012.…”

Section: Apoptotic Priming In Mitochondriamentioning

confidence: 99%

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Irwin

Moos

Faller

et al. 2016

Drug Development Research

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Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Apoptotic Priming In Mitochondriamentioning

confidence: 99%

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Irwin

Moos

Faller

et al. 2016

Drug Development Research

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“…Nonetheless, one possible explanation could be given by the fact that palmitoylcarnitine has been implicated in the pathology of ischemia, being a potent inhibitor of cardiac Na, K-ATPase. Due to its amphipathic character, palmitoylcarnitine can induce alterations in membrane fluidity and surface during apoptosis, and can change the activity of several enzymes and transmembrane transporters (Nalecz et al 2004). In this case, the membrane disturbance Metabolomics in NAION patients occurs in high-energy uptake cells of the optic nerve causing irreversible blindness.…”

Section: Metabolites As Potential Naion Biomarkersmentioning

confidence: 99%

Metabolomics in non-arteritic anterior ischemic optic neuropathy patients by liquid chromatography–quadrupole time-of-flight mass spectrometry

et al. 2014

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Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is a rare ischemic disease that affects the optic nerve. Pathophysiology and mechanism of ischemia of NAION remain uncertain, so the aim of this work is to establish the first metabolic fingerprinting of patients with NAION to discover possible new biomarkers. Twenty-four patients, aged 39-85 years, diagnosed with NAION, after a sudden loss of vision, were recruited for the study. Plasma samples of patients and controls were fingerprinted with liquid chromatography coupled to quadrupole time-offlight by electrospray ionization, and obtained data were filtered, aligned and statistically analysed to identify new biomarkers. The identity of compounds that were found to be significant in class separation was later confirmed by obtaining the characteristic MS/MS spectra and online databases. In general, biochemical and metabolic profiles between patients and controls did not show profound differences, but NAION patients presented disturbances in the phospholipid composition which lead to reduced plasma values of LysoPCs. Altered levels of other metabolites, such as L-Palmitoylcarnitine, have been detected and could be considered as potential biomarkers.

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“…-dependent cation/carnitine transporter and to a lesser extent via the B(0,?) amino acid transporter [6][7][8]; in particular, the drug has a brain uptake index of 2.4 ± 0.2, which is similar to that of GABA, indicating an affinity of L-acetylcarnitine for the GABA transport system [9].…”

Section: Introductionmentioning

confidence: 98%

Effect of In Vivo l-Acetylcarnitine Administration on ATP-ases Enzyme Systems of Synaptic Plasma Membranes from Rat Cerebral Cortex

2011

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The maximum rates (V (max)) of some enzymatic activities related to energy consumption (ATP-ases) were evaluated in two types of synaptic plasma membranes (SPM) isolated from cerebral cortex of rats subjected to in vivo treatment with L: -acetylcarnitine at two different doses (30 and 60 mg kg(-1) i.p., 28 days, 5 days/week). The following enzyme activities were evaluated: acetylcholinesterase (AChE); Na(+), K(+), Mg(2+)-ATP-ase; ouabain insensitive Mg(2+)-ATP-ase; Na(+), K(+)-ATP-ase; direct Mg(2+)-ATP-ase; Ca(2+), Mg(2+)-ATP-ase; Low- and High-affinity Ca(2+)-ATP-ase. Sub-chronic treatment with L: -acetylcarnitine increased Na(+), K(+)-ATP-ase activity on SPM 2 and Ca(2+), Mg(2+)-ATP-ase activity on both SPM fractions. These results suggest (1) that the sensitivity to drug treatment is different between the two populations of SPM, confirming the micro-heterogeneity of these sub-fractions, probably originating from different types of synapses, (2) the specificity of the molecular site of action of the drug on SPM and (3) its interference on ion homeostasis at synaptic level.

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Carnitine: transport and physiological functions in the brain

Cited by 95 publications

References 124 publications

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Metabolomics in non-arteritic anterior ischemic optic neuropathy patients by liquid chromatography–quadrupole time-of-flight mass spectrometry

Effect of In Vivo l-Acetylcarnitine Administration on ATP-ases Enzyme Systems of Synaptic Plasma Membranes from Rat Cerebral Cortex

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