The Evolution of Ketosis: Potential Impact on Clinical Conditions DOI Open Access

Latha Nagamani Dilliraj,

Giovanna Schiuma, Djidjell Lara

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(17), P. 3613 - 3613

Published: Sept. 1, 2022

Ketone bodies are small compounds derived from fatty acids that behave as an alternative mitochondrial energy source when insulin levels low, such during fasting or strenuous exercise. In addition to the metabolic function of ketone bodies, they also have several signaling functions separate production. this perspective, we review main current data referring in correlation with nutrition and pathways well potential impact on clinical conditions. Data were selected following eligibility criteria accordingly reviewed topic. We used a set electronic databases (Medline/PubMed, Scopus, Web Sciences (WOS), Cochrane Library) for systematic search until July 2022 using MeSH keywords/terms (i.e., BHB, acetoacetate, inflammation, antioxidant, etc.). The literature reported need confirmation consistent trials might validate results obtained vitro vivo animal models. However, exogenous consumption effect bodies' brain uptake metabolism spur research define acute chronic effects humans pursue possible implication prevention treatment human diseases. Therefore, additional studies required examine systemic consequences bodies.

Language: Английский

Mitochondrial heterogeneity and homeostasis through the lens of a neuron DOI
Gülçin Pekkurnaz, Xinnan Wang

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(7), P. 802 - 812

Published: July 11, 2022

Language: Английский

Citations

117
Glia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation DOI Creative Commons
Bryon Silva, Olivier L. Mantha,

Johann Schor

et al.

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(2), P. 213 - 224

Published: Feb. 17, 2022

Abstract During starvation, mammalian brains can adapt their metabolism, switching from glucose to alternative peripheral fuel sources. In the Drosophila starved brain, memory formation is subject adaptative plasticity, but whether this adaptive plasticity relies on metabolic adaptation remains unclear. Here we show that during neurons of fly olfactory centre import and use ketone bodies (KBs) as an energy substrate sustain aversive formation. We identify local providers within cortex glia, own lipid store synthesize KBs before exporting them via monocarboxylate transporters. Finally, master sensor AMP-activated protein kinase regulates both mobilization KB export in glia. Our data provide a general schema interactions brain support when scarce.

Language: Английский

Citations

96
Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum DOI
Renzo Guerrini, Valerio Conti, Massimo Mantegazza

et al.

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 433 - 513

Published: Aug. 11, 2022

Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe seizures EEG abnormalities on background developmental impairment that tends to worsen as consequence epilepsy. DEEs may result from both nongenetic genetic etiologies. Genetic have been associated with mutations in many genes involved different functions including cell migration, proliferation, organization, neuronal excitability, synapse transmission plasticity. Functional studies performed animal models clinical trials patients contributed elucidate pathophysiological mechanisms underlying explored the efficacy treatments. Here, we provide an extensive review phenotypic spectrum included determinants these conditions. We also brief overview most effective treatment now available emerging therapeutic approaches.

Language: Английский

Citations

96
Brain energy metabolism: A roadmap for future research DOI Creative Commons
Caroline Rae, Joseph A. Baur, Karin Borges

et al.

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

Citations

35
Mitochondrial heterogeneity and adaptations to cellular needs DOI
Melia Granath-Panelo, Shingo Kajimura

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 674 - 686

Published: May 1, 2024

Language: Английский

Citations

18
Understanding glucose metabolism and insulin action at the blood–brain barrier: Implications for brain health and neurodegenerative diseases DOI Creative Commons

Yiyi Zhu,

Alexei Verkhratsky, Hui Chen

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 16, 2025

The blood-brain barrier (BBB) is a highly selective, semipermeable critical for maintaining brain homeostasis. BBB regulates the transport of essential nutrients, hormones, and signaling molecules between bloodstream central nervous system (CNS), while simultaneously protecting from potentially harmful substances pathogens. This selective permeability ensures that nourished shielded toxins. An exception to this are regions, such as hypothalamus circumventricular organs, which irrigated by fenestrated capillaries, allowing rapid direct response various blood components. We overview metabolic functions BBB, with an emphasis on impact altered glucose metabolism insulin in pathogenesis neurodegenerative diseases. Notably, endothelial cells constituting exhibit distinct characteristics, primarily generating ATP through aerobic glycolysis. occurs despite their exposure abundant oxygen bloodstream, typically supports oxidative phosphorylation. effects astrocytes, form glial limitans component show marked sexual dimorphism. nutrient sensing hypothalamus, along signaling, systemic metabolism. Insulin modifies regulating expression tight junction proteins, angiogenesis, vascular remodeling, well modulating flow brain. disruptions particularly evident diseases, Alzheimer's disease Parkinson's disease, where breakdown accelerates cognitive decline. review highlights role normal functionality investigates how these pathways contribute onset progression

Language: Английский

Citations

3
Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions DOI Creative Commons
И. Ф. Беленичев, Olena Popazova, Nina Bukhtiyarova

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 108 - 108

Published: Jan. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Language: Английский

Citations

3
Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease DOI Creative Commons
Xin Zhang,

Nadine Alshakhshir,

Liqin Zhao

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: April 28, 2021

Alzheimer’s disease (AD) is the most common form of age-related dementia. Despite decades research, etiology and pathogenesis AD are not well understood. Brain glucose hypometabolism has long been recognized as a prominent anomaly that occurs in preclinical stage AD. Recent studies suggest glycolytic metabolism, cytoplasmic pathway breakdown glucose, may play critical role development Glycolysis essential for variety neural activities brain, including energy production, synaptic transmission, redox homeostasis. Decreased flux shown to correlate with severity amyloid tau pathology both clinical patients. Moreover, increased accumulation found brains patients supports hypothesis deficit be contributor this phenotype. hyperglycemia also provides plausible explanation well-documented link between diabetes. Humans possess three primary variants apolipoprotein E (ApoE) gene – ApoE ∗ ϵ2, ϵ3, ϵ4 confer differential susceptibility findings indicate neuronal glycolysis significantly affected by human isoforms robustness serve major mechanism renders an ApoE2-bearing brain more resistant against neurodegenerative risks In addition AD, dysfunction observed other diseases, Parkinson’s disease, Huntington’s amyotrophic lateral sclerosis, strengthening concept leading neurodegeneration. Taken together, these advances highlight promising translational opportunity involves targeting bolster metabolic resilience such alter course aging or prevent reduce only but diseases.

Language: Английский

Citations

80
Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions DOI Open Access
Maria Pina Mollica, Giovanna Trinchese, Fabiano Cimmino

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(4), P. 1111 - 1111

Published: March 28, 2021

Milk contains several important nutrients that are beneficial for human health. This review considers the nutritional qualities of essential fatty acids (FAs), especially omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated (PUFAs) present in milk from ruminant non-ruminant species. In particular, impact on metabolism is discussed, including its effects central nervous system. addition, we presented data indicating how animal feeding-the main way to modify fat composition-may have a potential health, rearing feeding systems strongly affect quality within same Finally, results vivo studies aimed at supporting FA intake models, factors limiting their transferability humans were discussed.

Language: Английский

Citations

73
Synapses: The Brain’s Energy-Demanding Sites DOI Open Access
Andreia Faria‐Pereira, Vanessa A. Morais

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3627 - 3627

Published: March 26, 2022

The brain is one of the most energy-consuming organs in mammalian body, and synaptic transmission major contributors. To meet these energetic requirements, primarily uses glucose, which can be metabolized through glycolysis and/or mitochondrial oxidative phosphorylation. relevance two energy production pathways fulfilling at presynaptic terminals has been subject recent studies. In this review, we dissect balance phosphorylation to demands both resting stimulation conditions. Besides ATP output needs, mitochondria synapse are also important for calcium buffering regulation reactive oxygen species. These mitochondrial-associated pathways, once hampered, impact negatively on neuronal homeostasis activity. Therefore, as assume a critical role homeostasis, it becoming evident that population possesses distinct functional fingerprint compared other mitochondria. Ultimately, dysregulation bioenergetics glycolytic dysfunctions increasingly implicated neurodegenerative disorders, first hallmarks several diseases deficits, followed by degeneration.

Language: Английский

Citations

69