Mitochondria in the elderly: Is acetylcarnitine a rejuvenator?☆

Roșca, Mariana G.; Lemieux, Hélène; Hoppel, Charles L.

doi:10.1016/j.addr.2009.06.009

Cited by 76 publications

(70 citation statements)

References 155 publications

(208 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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“…Increasing mitochondrial antioxidant activities by elevating mitochondrial reducing power is considered as an important mechanism of neuroprotection by several naturally occurring compounds, including ketone bodies, pyruvate, and acyl-carnitines (Ryu et al, 2004;Zanelli et al, 2005;Gasior et al, 2006;Zhao et al, 2006b;Jarrett et al, 2008;Rosca et al, 2009;Alves et al, 2009;Jones et al, 2010;Zhang et al, 2010). This mechanism of action might be particularly important during reperfusion after cerebral ischemia, when the mitochondrial redox state is hyperoxidized, ROS production is elevated, and there are increased markers of oxidative molecular modification (Perez-Pinzon et al, 1999;Fiskum et al, 2004).…”

Section: Protection Against Mitochondrial Oxidative Stressmentioning

confidence: 99%

Novel Mitochondrial Targets for Neuroprotection

Pérez-Pinzón

Stetler

Fiskum

2012

J Cereb Blood Flow Metab

130

108

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Mitochondrial dysfunction contributes to the pathophysiology of acute neurologic disorders and neurodegenerative diseases. Bioenergetic failure is the primary cause of acute neuronal necrosis, and involves excitotoxicity-associated mitochondrial Ca 2 + overload, resulting in opening of the inner membrane permeability transition pore and inhibition of oxidative phosphorylation. Mitochondrial energy metabolism is also very sensitive to inhibition by reactive O 2 and nitrogen species, which modify many mitochondrial proteins, lipids, and DNA/RNA, thus impairing energy transduction and exacerbating free radical production. Oxidative stress and Ca 2 + -activated calpain protease activities also promote apoptosis and other forms of programmed cell death, primarily through modification of proteins and lipids present at the outer membrane, causing release of proapoptotic mitochondrial proteins, which initiate caspase-dependent and caspase-independent forms of cell death. This review focuses on three classifications of mitochondrial targets for neuroprotection. The first is mitochondrial quality control, maintained by the dynamic processes of mitochondrial fission and fusion and autophagy of abnormal mitochondria. The second includes targets amenable to ischemic preconditioning, e.g., electron transport chain components, ion channels, uncoupling proteins, and mitochondrial biogenesis. The third includes mitochondrial proteins and other molecules that defend against oxidative stress. Each class of targets exhibits excellent potential for translation to clinical neuroprotection.

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“…Mitochondrial ALC has been reported to provide acetyl groups for nuclear histone acetylation suggesting this as one of its mechanisms of action (Madiraju et al 2009). The ALC action on gene expression might explain the reported role of ALC in intermediate and mitochondrial metabolism as well as its trophic and antioxidant actions (Rosca et al 2009). …”

Section: Mitochondria-targeted Chemopreventionmentioning

confidence: 99%

Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome

et al. 2010

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Oxidative stress is a phenotypic hallmark in several genetic disorders characterized by cancer predisposition and/or propensity to premature ageing. Here we review the published evidence for the involvement of oxidative stress in the phenotypes of Ataxia-Telangiectasia (A-T), Down Syndrome (DS), Fanconi Anaemia (FA), and Werner Syndrome (WS), from the viewpoint of mitochondrial dysfunction. Mitochondria are recognized as both the cell compartment where energetic metabolism occurs and as the first and most susceptible target of reactive oxygen species (ROS) formation. Thus, a critical evaluation of the basic mechanisms leading to an in vivo pro-oxidant state relies on elucidating the features of mitochondrial impairment in each disorder. The evidence for different mitochondrial dysfunctions reported in A-T, DS, and FA is reviewed. In the case of WS, clear-cut evidence linking human WS phenotype to mitochondrial abnormalities is lacking so far in the literature. Nevertheless, evidence relating mitochondrial dysfunctions to normal ageing suggests that WS, as a progeroid syndrome, is likely to feature mitochondrial abnormalities. Hence, ad hoc research focused on elucidating the nature of mitochondrial dysfunction in WS pathogenesis is required. Based on the recognized, or reasonably suspected, role of mitochondrial abnormalities in the pathogenesis of these disorders, studies of chemoprevention with mitochondria-targeted supplements are warranted.

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Mitochondria in the elderly: Is acetylcarnitine a rejuvenator?☆

Cited by 76 publications

References 155 publications

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Novel Mitochondrial Targets for Neuroprotection

Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome

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