Nrf2 deficiency increases oligodendrocyte loss, demyelination, neuroinflammation and axonal damage in an MS animal model

Nellessen, Anna; Nyamoya, Stella; Zendedel, Adib; Slowik, Alexander; Wruck, Christoph Jan; Beyer, Cordian; Fragoulis, Athanassios; Clarner, Tim

doi:10.1007/s11011-019-00488-z

Cited by 39 publications

(24 citation statements)

References 48 publications

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“…[21][22][23] Now, the NVU is a tool that can be used to understand normal brain physiology as well as the pathophysiology of numerous neurological disorders. [24][25][26][27][28][29] Conversely, the malfunction of astroglia in the NVU (i.e., "astrogliopathy") [30][31][32][33][34] induces neuronal dysfunction, leading to various neurological disorders including cerebrovascular disease (e.g., stroke and small vessel disease-like Binswanger's disease and cerebral autosomaldominant arteriopathy with subcortical infarct and leukoencephalopathy [CADASIL]/ 35 cerebral autosomal recessive arteriopathy with subcortical infarct and leukoencephalopathy [CARASIL]), 36,37 neurodegenerative disease (e.g., Alzheimer's disease, 38,39 Parkinson's disease, 40,41 and amyotrophic lateral sclerosis [ALS]), [42][43][44] and neuroimmunological disease (e.g., multiple sclerosis [MS], [45][46][47][48] and neuromyelitis optica spectrum disorder [NMOSD]). 49,50 This review will focus on the supportive roles of astroglia in the NVU from the perspective of three major metabolic compartments with neurons: (i) glucose and lactate; (ii) fatty acid and ketone bodies (KBs); and (iii) D-and L-serine.…”

Section: Introductionmentioning

confidence: 99%

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and microvasculature in the brain gray matter. They play a pivotal role in brain metabolism as well as in the regulation of cerebral blood flow, taking advantage of their unique anatomical location. In particular, the astroglial cellular metabolic compartment exerts supportive roles in dedicating neurons to the generation of action potentials and protects them against oxidative stress associated with their high energy consumption. An impairment of normal astroglial function, therefore, can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuroimmunological diseases, in which metabolic derangements accelerate neuronal damage. The neurovascular unit (NVU), the major components of which include neurons, microvessels, and astroglia, is a conceptual framework that was originally used to better understand the pathophysiology of cerebral ischemia. At present, the NVU is a tool for understanding normal brain physiology as well as the pathophysiology of numerous neurological disorders. The metabolic responses of astroglia in the NVU can be either protective or deleterious. This review focuses on three major metabolic compartments: (i) glucose and lactate; (ii) fatty acid and ketone bodies; and (iii) D‐ and L‐serine. Both the beneficial and the detrimental roles of compartmentalization between neurons and astroglia will be discussed. A better understanding of the astroglial metabolic response in the NVU is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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“…Therefore, the downregulation of NRF2 expression appears to be a cellular event that promotes the shift from lesions resolving to lesion-promoting astrocytes. Consistent with this, the metabolic injury to oligodendrocytes that were experimentally induced via intoxication with cuprizone [ 38 ] is increased in Nrf2 −/− compared to wild-type mice [ 39 ], while the activation of NRF2, especially in GFAP + astrocytes, improved the pathology in a toxin-induced demyelination model [ 40 ].…”

Section: General Aspects Of Ms Pathology and The Relevance Of Gliamentioning

confidence: 84%

Does Siponimod Exert Direct Effects in the Central Nervous System?

Kipp

2020

Cells

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The modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes in lymph nodes. Different sphingosine 1-phosphate receptor subtypes are expressed in the brain and spinal cord, and their pharmacological effects may improve disease development and neuropathology. Siponimod (BAF312) is a novel sphingosine 1-phosphate receptor modulator that has recently been approved for the treatment of active secondary progressive multiple sclerosis (MS). In this review article, we summarize recent evidence suggesting that the active role of siponimod in patients with progressive MS may be due to direct interaction with central nervous system cells. Additionally, we tried to summarize our current understanding of the function of siponimod and discuss the effects observed in the case of MS.

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“…[31] The exact mechanism by which MeD may be protective in neurodegenerative disorders is yet unknown. Oxidative stress -as a result of imbalance in pro-oxidant/antioxidant homeostasis -has been implicated in the pathogenesis of MS. [32] Complex phenols and other substances, including vitamin C, vitamin E, and carotenoids may serve as antioxidants and are found in high concentrations in the various forms of the MeD.…”

Section: Discussionmentioning

confidence: 99%

Potential of modified Mediterranean diet to improve quality of life and fatigue severity in multiple sclerosis patients: a single-center randomized controlled trial

Moravejolahkami

Paknahad

Chitsaz

et al. 2020

International Journal of Food Properties

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Nrf2 deficiency increases oligodendrocyte loss, demyelination, neuroinflammation and axonal damage in an MS animal model

Cited by 39 publications

References 48 publications

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Does Siponimod Exert Direct Effects in the Central Nervous System?

Potential of modified Mediterranean diet to improve quality of life and fatigue severity in multiple sclerosis patients: a single-center randomized controlled trial

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