Brain Glucose Metabolism: Integration of Energetics with Function

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 949 - 1045

Published: Dec. 19, 2018

Glucose is the long-established, obligatory fuel for brain that fulfills many critical functions, including ATP production, oxidative stress management, and synthesis of neurotransmitters, neuromodulators, structural components. Neuronal glucose oxidation exceeds in astrocytes, but both rates increase direct proportion to excitatory neurotransmission; signaling metabolism are closely coupled at local level. Exact details neuron-astrocyte glutamate-glutamine cycling remain be established, specific roles lactate cellular energetics these processes debated. Glycolysis preferentially upregulated during activation even though oxygen availability sufficient (aerobic glycolysis). Three major pathways, glycolysis, pentose phosphate shunt, glycogen turnover, contribute utilization excess oxygen, adrenergic regulation aerobic glycolysis draws attention astrocytic metabolism, particularly which has a high impact on oxygen-carbohydrate mismatch. Aerobic proposed predominant young children regions, re-evaluation data necessary. Shuttling glucose- glycogen-derived from astrocytes neurons activation, neurotransmission, memory consolidation controversial topics alternative mechanisms proposed. Nutritional therapy vagus nerve stimulation translational bridges clinical treatment diverse disorders.

Language: Английский

---

NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases

Redox Biology, Journal Year: 2021, Volume and Issue: 41, P. 101947 - 101947

Published: March 20, 2021

Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Mitochondrial dysfunction is linked to oxidative and reactive oxygen species (ROS) neurotoxicity during AD. Impaired mitochondrial metabolism associated with brain damage While role NADPH oxidase 4 (NOX4), a major source ROS, identified damage, mechanism by which NOX4 regulates ferroptosis astrocytes AD remains unclear. Here, we show that protein levels were significantly elevated impaired cerebral cortex from patients APP/PS1 double-transgenic mouse model The 4-hydroxynonenal (4-HNE) malondialdehyde (MDA), marker stress-induced lipid peroxidation, also We demonstrate over-expression increases impairment inhibition respiration ATP production via reduction five complexes ETC human astrocytes. Moreover, elevation induces ROS (mtROS) production, fragmentation, cellular antioxidant process Furthermore, increased ferroptosis-dependent cytotoxicity activation peroxidation These results suggest promotes

Language: Английский

---

The role of astrocytes in oxidative stress of central nervous system: A mixed blessing

Cell Proliferation, Journal Year: 2020, Volume and Issue: 53(3)

Published: Feb. 8, 2020

Abstract Central nervous system (CNS) maintains a high level of metabolism, which leads to the generation large amounts free radicals, and it is also one most vulnerable organs oxidative stress. Emerging evidences have shown that, as key homeostatic cells in CNS, astrocytes are deeply involved multiple aspects CNS function including stress regulation. Besides, redox can turn affect morphology function. The complex roles indicate that their correct performance crucial for normal functioning its dysfunction may result occurrence progression various neurological disorders. To date, influence rarely reviewed. Therefore, this review we sum up regulation corresponding mechanisms under both different pathological conditions.

Language: Английский

---

Mitophagy: Molecular Mechanisms, New Concepts on Parkin Activation and the Emerging Role of AMPK/ULK1 Axis

Cells, Journal Year: 2021, Volume and Issue: 11(1), P. 30 - 30

Published: Dec. 23, 2021

Mitochondria are multifunctional subcellular organelles essential for cellular energy homeostasis and apoptotic cell death. It is, therefore, crucial to maintain mitochondrial fitness. Mitophagy, the selective removal of dysfunctional mitochondria by autophagy, is critical regulating quality control in many physiological processes, including development differentiation. On other hand, both impaired excessive mitophagy involved pathogenesis different ageing-associated diseases such as neurodegeneration, cancer, myocardial injury, liver disease, sarcopenia diabetes. The best-characterized pathway PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent pathway. However, Parkin-independent pathways also reported mediate tethering autophagy apparatuses, directly activating (mitophagy receptors E3 ligases). In addition, existence molecular mechanisms than PINK1-mediated phosphorylation Parkin activation was proposed. adenosine5′-monophosphate (AMP)-activated protein (AMPK) emerging a key player metabolism mitophagy. Beyond its involvement fission autophagosomal engulfment, interplay with PINK1–Parkin reported. Here, we review recent advances elucidating canonical signaling that regulate mitophagy, focusing on early role spatial specificity AMPK/ULK1 axis.

Language: Английский

---

Mitochondria, energy, and metabolism in neuronal health and disease

FEBS Letters, Journal Year: 2022, Volume and Issue: 596(9), P. 1095 - 1110

Published: Jan. 28, 2022

Mitochondria are associated with various cellular activities critical to homeostasis, particularly in the nervous system. The plastic architecture of mitochondrial network and its dynamic structure play crucial roles ensuring that varying energetic demands rapidly met maintain neuronal axonal energy homeostasis. Recent evidence associates aging neurodegeneration anomalous metabolism as age‐dependent alterations now believed occur prior neurodegeneration. brain has a high demand, which makes it sensitive dysfunction. Distinct events causing oxidative stress or disruption homeostasis can trigger neuropathology. This review explores bioenergetic hypothesis for neurodegenerative pathomechanisms, discussing factors leading age‐related hypometabolism contribution cognitive decline. research on healthy system cells, response stress, how is affected by pathology, well current contributions novel therapeutic approaches will be highlighted.

Language: Английский

---

Ginsenoside Rb1 inhibits astrocyte activation and promotes transfer of astrocytic mitochondria to neurons against ischemic stroke

Redox Biology, Journal Year: 2022, Volume and Issue: 54, P. 102363 - 102363

Published: June 8, 2022

Astrocytes activation in response to stroke results altered mitochondrial exchange with neurons. Ginsenoside Rb1is a major ginsenoside of Panax ginseng particularly known for its neuroprotective potential. This work aimed investigate if Rb1 could rescue neurons from ischemic insult via astrocyte inactivation and transfer. We prepared conditioned astrocytes-derived medium co-culture examined the role transfer astrocytes The potential was further confirmed vivo using mouse model brain ischemia. In oxygen-glucose deprivation reperfusion (OGD/R), were reactivated produced reactive oxygen species (ROS), an action that blocked by Rb1. Mechanistically, inhibited NADH dehydrogenase complex I block reverse electron transport-derived ROS production I, thus inactivated protect mitochondria. Mitochondrial signal, membrane ATP detected astrocyte-derived indicated protected functional mitochondria facilitated their When injured OGD/R insult, co-culturing increased consumption rate within neurons, indicating protection conferred on them astrocytes. Using model, CD38 knockdown cerebral ventricles diminished effects Rb1, providing evidence support Transient inhibition reduced consequently avoided activation. Astrocyte therefore seemed means which promote neuronal survival function. Different neurocentric view, these findings suggest may be promising target pharmacological interventions injury.

Language: Английский

---

Astrocyte metabolism and signaling pathways in the CNS

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

---

Brain energy metabolism: A roadmap for future research

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: 168(5), P. 910 - 954

Published: Jan. 6, 2024

Although we have learned much about how the brain fuels its functions over last decades, there remains still to discover in an organ that is so complex. This article lays out major gaps our knowledge of interrelationships between metabolism and function, including biochemical, cellular, subcellular aspects functional imaging adult brain, as well during development, aging, disease. The focus on unknowns substrates associated transporters, roles insulin lipid droplets, emerging role microglia, mysteries cofactor signaling molecule NAD

Language: Английский

---

NRF2 Deficiency Promotes Ferroptosis of Astrocytes Mediated by Oxidative Stress in Alzheimer’s Disease

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7517 - 7533

Published: Feb. 24, 2024

Language: Английский

---

The Glutamate/GABA‐Glutamine Cycle: Insights, Updates, and Advances

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(3)

Published: March 1, 2025

ABSTRACT Synaptic homeostasis of the principal neurotransmitters glutamate and GABA is tightly regulated by an intricate metabolic coupling between neurons astrocytes known as glutamate/GABA‐glutamine cycle. In this cycle, take up from synapse convert these into glutamine. Astrocytic glutamine subsequently transferred to neurons, serving precursor for neuronal synthesis. The cycle integrates multiple cellular processes, including neurotransmitter release, uptake, synthesis, metabolism. All processes are deeply interdependent closely coupled energy Astrocytes display highly active mitochondrial oxidative metabolism several unique features, glycogen storage pyruvate carboxylation, which essential sustain continuous release. However, new roles oligodendrocytes microglia in recycling emerging. Malfunction can lead severe synaptic disruptions may be implicated brain diseases. Here, I review central aspects recent advances highlight how functionally connected critical functions First, overview glutamate, GABA, transport provided relation recycling. Then, reviewed, with a special emphasis on glial cells. Finally, discuss aberrant linked neurodegeneration disease, focusing astrocyte dysfunction lipid emerging pathological mechanisms. Instead viewing individual biochemical more holistic integrative approach needed advance our understanding modulates function both health disease. image

Language: Английский

---