Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour

Vicente-Gutiérrez, Carlos; Bonora, Nicolo; Bobo-Jiménez, Verónica; Jiménez-Blasco, Daniel; López-Fabuel, Irene; Fernández, Emilio; Joséphine, Charlène; Bonvento, Gilles; Enríquez, José Antonio; Almeida, Ángeles; Bolaños, Juan P.

doi:10.1038/s42255-018-0031-6

Cited by 138 publications

(155 citation statements)

References 47 publications

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“…Reactive oxygen species (ROS) are a by-product of mitochondrial activity and at high levels can cause oxidative stress in the cell. Despite the negative impact of excess ROS on cellular stress, ROS production by astrocytes may have a role in regulating normal CNS function ( Vicente-Gutierrez et al, 2019 ). Astrocytes cultured from mice with astrocyte-specific down-regulation of ROS production had altered cellular metabolism: glycolysis was reduced while activity of the PPP increased, and a lower NADPH(H + )/NADP + ratio was observed.…”

Section: Metabolic Changes In Glia Are Implicated In Modifying Behavimentioning

confidence: 99%

“…Astrocytes cultured from mice with astrocyte-specific down-regulation of ROS production had altered cellular metabolism: glycolysis was reduced while activity of the PPP increased, and a lower NADPH(H + )/NADP + ratio was observed. In vivo, mice with reduced astrocytic ROS production displayed altered neuronal dendrite projections in the hippocampus and parietal cortex, alongside cognitive impairment ( Vicente-Gutierrez et al, 2019 ). While accumulation of ROS can be pathological when dysregulated, this aforementioned study and others ( Angelova and Abramov, 2016 ) implicate astrocytic ROS production as a part of normal physiological regulation of cellular signalling pathways.…”

Section: Metabolic Changes In Glia Are Implicated In Modifying Behavimentioning

confidence: 99%

“…There is developing evidence that immunometabolic changes are also seen in glia (most notably microglia ( Paolicelli and Angiari, 2019 ) and astrocytes ( Vicente-Gutierrez et al, 2019 )). Although not yet as comprehensively studied as in peripheral immune cells, these are potential therapeutic targets for neurological disease.…”

Section: Introductionmentioning

confidence: 99%

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Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

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Section: Metabolic Changes In Glia Are Implicated In Modifying Behavimentioning

confidence: 99%

Section: Metabolic Changes In Glia Are Implicated In Modifying Behavimentioning

confidence: 99%

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Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

et al. 2020

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“…Cln7 Δ ex2 mice were thus crossed with mice expressing a mitochondrial tagged isoform of the H 2 O 2 -detoxifying enzyme catalase (mCAT) governed by the neuron-specific 17 calcium/calmodulin-dependent protein kinase II alpha (CaMKIIa) promoter ( CaMKIIa Cre -mCAT LoxP ). mCAT efficacy in vivo was previously validated 18 . The resulting progeny ( Cln7 Δex2 -CAMKIIa Cre -mCAT ) was analyzed and compared with littermate Cln7 Δex2 -mCAT LoxP and control ( mCAT Lop and CAMKIIa Cre -mCAT) mice.…”

mentioning

confidence: 99%

“…Mitochondrial ROS stimulate brain glucose consumption through the glycolytic pathway in mouse 18 . In Cln7 Δex2 -mCAT LoxP neurons, both glycolysis ( Fig.…”

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confidence: 99%

Mitochondrial collapse links PFKFB3-promoted glycolysis with CLN7/MFSD8 neuronal ceroid lipofuscinosis pathogenesis

López-Fabuel

García-Macia

Buondelmonte

et al. 2020

Preprint

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The neuronal ceroid lipofuscinoses (NCLs) are a family of monogenic life-limiting pediatric neurodegenerative disorders collectively known as Batten disease. Although genetically heterogeneous, NCLs share several clinical symptoms and pathological hallmarks such as lysosomal accumulation of lipofuscin and astrogliosis. CLN7 disease belongs to a group of NCLs that present in late infancy4-6 and, whereas CLN7/MFSD8 gene is known to encode a lysosomal membrane glycoprotein, the biochemical processes affected by CLN7-loss of function are unexplored thus preventing development of potential treatments. Here, we found in the Cln7Δex2 mouse model11 of CLN7 disease that failure in the autophagy-lysosomal pathway causes accumulation of structurally and bioenergetically impaired, reactive oxygen species (ROS)-producing neuronal mitochondria that contribute to CLN7 pathogenesis. Cln7Δex2 neurons exhibit a metabolic shift mediated by pro-glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3). PFKFB3 inhibition in Cln7Δex2 mice in vivo and in CLN7 patients-derived cells rectified key disease hallmarks. Thus, specifically targeting glycolysis may alleviate CLN7 pathogenesis.

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Construction of Nanoscale Covalent Organic Frameworks via Photocatalysis‐Involved Cascade Reactions for Tumor‐Selective Treatment

Zhou

Dong

2021

Advanced Therapeutics

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Photocatalysis is a powerful tool in modern organic synthesis, however, it has not been applied to the synthesis of covalent organic frameworks (COFs), even in synthetic cascade approaches. Herein, the construction of a series of imine-linked COFs from benzyl ethers and aromatic amines via sequential visible-light-induced photocatalytic oxidation and imine condensation steps is reported. The synthesis is performed under ambient conditions and is readily expanded to the gram-scale. This strategy results in imine-linked COFs possessing a uniform particle size with regular spherical morphology which may be particularly suitable for biomedical applications. This is an improvement to the conventional solvothermal method which results in heterogenous particles. For example, RT-COF-1 synthesized in this work is a promising nanocarrier for loading lonidamine for selective tumor treatment via chemotherapy. It is believed that the concept of photocatalytic-cascade COF synthesis expands the scope for imine-linked COFs and significantly enriches the nanoscale COF synthetic methodology.

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Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour

Cited by 138 publications

References 47 publications

Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

Immunometabolic Changes in Glia – A Potential Role in the Pathophysiology of Obesity and Diabetes

Mitochondrial collapse links PFKFB3-promoted glycolysis with CLN7/MFSD8 neuronal ceroid lipofuscinosis pathogenesis

Construction of Nanoscale Covalent Organic Frameworks via Photocatalysis‐Involved Cascade Reactions for Tumor‐Selective Treatment

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