MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis

Srinivasan, Radhika; Ratiney, H.; Hammond-Rosenbluth, Kathyrn E.; Pelletier, Daniel; Nelson, Sarah J.

doi:10.1016/j.mri.2009.06.008

Cited by 116 publications

(119 citation statements)

References 32 publications

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“…This runs counter to the findings reported in clinical and experimental studies of nerve tissue and cerebrospinal fluid [28][29][30][31]; Di Giussepe et al also observed no statistically-significant difference in GSH levels between RR-MS patients and healthy controls [32]. This apparent discrepancy may be due to the nature of the sample (tissue, cerebrospinal fluid, plasma or erythrocytes), to differences in the study situation (experimental models and clinical studies with different characteristics) and/or to patient-specific features.…”

Section: Discussioncontrasting

confidence: 86%

Peripheral oxidative stress in relapsing–remitting multiple sclerosis

Tasset

Agüera

Sánchez-López

et al. 2012

Clinical Biochemistry

104

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Section: Discussioncontrasting

confidence: 86%

Peripheral oxidative stress in relapsing–remitting multiple sclerosis

Tasset

Agüera

Sánchez-López

et al. 2012

Clinical Biochemistry

104

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“…Elucidation of this pathway suggests a potential role for cell type-specific neuroprotective responses and is consistent with the astrocyte data presented here. It is clear that increasing cellular GSH levels in the CNS could have a meaningful therapeutic impact on MS, because reduced brain GSH levels have been reported in patients with MS, as measured by magnetic resonance spectroscopy (Srinivasan et al, 2010;Choi et al, 2011). Therapies in clinical trials for MS, such as BG-12, which is an oral therapeutic containing DMF as the active ingredient (which is quantitatively converted to MMF after oral DMF delivery), could increase cellular GSH levels ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Fumarates Promote Cytoprotection of Central Nervous System Cells against Oxidative Stress via the Nuclear Factor (Erythroid-Derived 2)-Like 2 Pathway

Scannevin

Chollate

Jung

et al. 2012

J Pharmacol Exp Ther

413

382

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Oxidative stress is central to the pathology of several neurodegenerative diseases, including multiple sclerosis, and therapeutics designed to enhance antioxidant potential could have clinical value. The objective of this study was to characterize the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and further explore the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Treatment of animals or primary cultures of CNS cells with DMF or MMF resulted in increased nuclear levels of active Nrf2, with subsequent up-regulation of canonical antioxidant target genes. DMF-dependent up-regulation of antioxidant genes in vivo was lost in mice lacking Nrf2 [Nrf2(Ϫ/Ϫ)]. DMF or MMF treatment increased cellular redox potential, glutathione, ATP levels, and mitochondrial membrane potential in a concentration-dependent manner. Treating astrocytes or neurons with DMF or MMF also significantly improved cell viability after toxic oxidative challenge in a concentration-dependent manner. This effect on viability was lost in cells that had eliminated or reduced Nrf2. These data suggest that DMF and MMF are cytoprotective for neurons and astrocytes against oxidative stress-induced cellular injury and loss, potentially via up-regulation of an Nrf2-dependent antioxidant response. These data also suggest DMF and MMF may function through improving mitochondrial function. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic containing DMF as the active ingredient.

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“…Recent developments in MRS spectra have enabled in vivo quantification of GSH from specific brain regions [81]. Only a small handful of studies have assessed in vivo brain GSH levels by MRS in patients with CNS conditions-epilepsy [83,84], schizophrenia [85][86][87], multiple sclerosis [88,89], bipolar disorder [90,91], and mood depressive disorder [91,92]. Recent work has added to this body of work by assessing GSH levels in brains of MCI and AD patients [68,69].…”

Section: Potential Of Gsh Quantitation With Mrs As a Biomarkermentioning

confidence: 99%

The Emerging Role of Glutathione in Alzheimer's Disease

Saharan

Mandal

2014

JAD

154

100

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With millions of older individuals presently suffering from Alzheimer's disease (AD) worldwide, AD is an unduly common form of dementia that exacts a heavy toll on affected individuals and their families. One of the emerging causative factors associated with AD pathology is oxidative stress. This AD-related increase in oxidative stress has been attributed to decreased levels of the brain antioxidant, glutathione (GSH). In this article, we review the role of GSH in AD from a pathological as well as a diagnostic point of view. We recapitulate the literature that has assessed the role of GSH in AD onset and progression. We discuss the various methodologies through which alterations in GSH levels might be monitored, and highlight the yet uncharted potential of assaying GSH levels in vivo with magnetic resonance spectroscopy in AD therapeutics and prognostics. Finally, the present manuscript integrates findings from various studies to elucidate the possible molecular mechanisms through which disruptions in GSH homeostasis may contribute to AD pathology.

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MR spectroscopic imaging of glutathione in the white and gray matter at 7 T with an application to multiple sclerosis

Cited by 116 publications

References 32 publications

Peripheral oxidative stress in relapsing–remitting multiple sclerosis

Peripheral oxidative stress in relapsing–remitting multiple sclerosis

Fumarates Promote Cytoprotection of Central Nervous System Cells against Oxidative Stress via the Nuclear Factor (Erythroid-Derived 2)-Like 2 Pathway

The Emerging Role of Glutathione in Alzheimer's Disease

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