The Role of Acyl-CoA β-Oxidation in Brain Metabolism and Neurodegenerative Diseases

This review highlights the complex role of fatty acid β-oxidation in brain metabolism. It demonstrates the fundamental importance of fatty acid degradation as a fuel in energy balance and as an essential component in lipid homeostasis, brain aging, and neurodegenerative disorders.

[1]  C. Matute,et al.  Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis , 2023, International journal of molecular sciences.

[2]  Z. Sheng,et al.  Oligodendrocyte-derived transcellular signaling regulates axonal energy metabolism , 2023, Current Opinion in Neurobiology.

[3]  A. Raikes,et al.  Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration , 2023, Nature Metabolism.

[4]  M. Ioannou,et al.  Astrocytic OxPhos: more than just energy production , 2023, Nature Metabolism.

[5]  M. Tétreault,et al.  Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration , 2022, Communications Biology.

[6]  Yi Wang,et al.  Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease , 2022, Journal of Neuroinflammation.

[7]  Jie Zhang,et al.  Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases , 2022, CNS neuroscience & therapeutics.

[8]  M. Palkovits,et al.  Mitochondrial dysfunction is a key pathological driver of early stage Parkinson’s , 2022, Acta neuropathologica communications.

[9]  Lieliang Zhang,et al.  Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases , 2022, Cell & bioscience.

[10]  G. Peluso,et al.  The Reversible Carnitine Palmitoyltransferase 1 Inhibitor (Teglicar) Ameliorates the Neurodegenerative Phenotype in a Drosophila Huntington’s Disease Model by Acting on the Expression of Carnitine-Related Genes , 2022, Molecules.

[11]  F. Yin.  Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise , 2022, The FEBS journal.

[12]  S. Erramilli,et al.  Structural basis of omega-3 fatty acid transport across the blood–brain barrier , 2021, Nature.

[13]  T. Amen,et al.  Stress granules inhibit fatty acid oxidation by modulating mitochondrial permeability , 2021, Cell reports.

[14]  G. Reiser,et al.  How the brain fights fatty acids’ toxicity , 2021, Neurochemistry International.

[15]  J. Kong,et al.  Ketogenic diet protects myelin and axons in diffuse axonal injury , 2021, Nutritional neuroscience.

[16]  Shirisha Nagotu,et al.  Peroxisomes of the Brain: Distribution, Functions, and Associated Diseases , 2021, Neurotoxicity Research.

[17]  Xiaojian Shi,et al.  ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism , 2021, Cell reports.

[18]  R. Franco,et al.  Mitochondrial Metabolism in Astrocytes Regulates Brain Bioenergetics, Neurotransmission and Redox Balance , 2020, Frontiers in Neuroscience.

[19]  J. Rungby,et al.  Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases , 2020, International journal of molecular sciences.

[20]  P. Ivanov,et al.  Molecular mechanisms of stress granule assembly and disassembly. , 2020, Biochimica et biophysica acta. Molecular cell research.

[21]  M. Ioannou,et al.  Current Insights into Fatty Acid Transport in the Brain , 2020, The Journal of Membrane Biology.

[22]  M. Mann,et al.  Cell-Type- and Brain-Region-Resolved Mouse Brain Lipidome. , 2020, Cell reports.

[23]  Jing Qu,et al.  Protein acetylation and deacetylation: An important regulatory modification in gene transcription (Review) , 2020, Experimental and therapeutic medicine.

[24]  M. Mattson,et al.  Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing , 2020, Nature Reviews Drug Discovery.

[25]  L. McCullough,et al.  Peroxisomal Dysfunction in Neurological Diseases and Brain Aging , 2020, Frontiers in Cellular Neuroscience.

[26]  Shinichi Takahashi.  Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit , 2020, Neuropathology : official journal of the Japanese Society of Neuropathology.

[27]  S. Spiegel,et al.  Functional analysis of molecular and pharmacological modulators of mitochondrial fatty acid oxidation , 2020, Scientific Reports.

[28]  J. Bogie,et al.  Fatty acid metabolism in the progression and resolution of CNS disorders. , 2020, Advanced drug delivery reviews.

[29]  F. Yin,et al.  Cellular Specificity and Inter-cellular Coordination in the Brain Bioenergetic System: Implications for Aging and Neurodegeneration , 2020, Frontiers in Physiology.

[30]  Yunjong Lee,et al.  The regulation of glutamic acid decarboxylases in GABA neurotransmission in the brain , 2019, Archives of Pharmacal Research.

[31]  J. Pedraza-Chaverri,et al.  Ketone bodies, stress response, and redox homeostasis , 2019, Redox biology.

[32]  S. Tucci,et al.  Therapeutic potential of triheptanoin in metabolic and neurodegenerative diseases , 2019, Journal of inherited metabolic disease.

[33]  A. Konnerth,et al.  Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity , 2019, Nature Neuroscience.

[34]  E. Gratton,et al.  Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice. , 2019, Cell metabolism.

[35]  J. Lippincott-Schwartz,et al.  Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity , 2019, Cell.

[36]  K. Whittingstall,et al.  A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment , 2019, Alzheimer's & Dementia.

[37]  A. Sinclair,et al.  Plasmalogens and Alzheimer’s disease: a review , 2019, Lipids in Health and Disease.

[38]  D. Michaelson,et al.  ApoE4: an emerging therapeutic target for Alzheimer’s disease , 2019, BMC Medicine.

[39]  Michael D. Greicius,et al.  A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward , 2019, Neuron.

[40]  M. Kreft,et al.  Metabolic Plasticity of Astrocytes and Aging of the Brain , 2019, International journal of molecular sciences.

[41]  D. Langford,et al.  Astrocyte activation and altered metabolism in normal aging, age-related CNS diseases, and HAND , 2019, Journal of NeuroVirology.

[42]  A. Pulvirenti,et al.  A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses , 2018, Front. Psychiatry.

[43]  Mikko T. Huuskonen,et al.  PPARβ/δ‐agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes , 2018, Glia.

[44]  E. Galea,et al.  GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes , 2018, Glia.

[45]  Ghulam Md Ashraf,et al.  APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis , 2018, Molecular Neurobiology.

[46]  J. Wiśniewski,et al.  Aging‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle , 2018, Glia.

[47]  E. Wolvetang,et al.  Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease , 2018, Front. Mol. Neurosci..

[48]  D. Wallace,et al.  Mitochondrial Etiology of Neuropsychiatric Disorders , 2017, Biological Psychiatry.

[49]  P. Carmeliet,et al.  A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity , 2017, Cell reports.

[50]  Caitlyn E. Bowman,et al.  Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain , 2017, Journal of neurochemistry.

[51]  P. Bickford,et al.  Proteomic anaysis of aged microglia: shifts in transcription, bioenergetics, and nutrient response , 2017, Journal of Neuroinflammation.

[52]  Sheue-yann Cheng,et al.  Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage , 2017, Journal of Cerebral Blood Flow and Metabolism.

[53]  R. Wanders,et al.  “Role of peroxisomes in human lipid metabolism and its importance for neurological development” , 2017, Neuroscience Letters.

[54]  C. Dotti,et al.  Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age , 2016, PloS one.

[55]  D. Turnbull,et al.  Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells , 2016, Neuro-oncology.

[56]  G. Reiser,et al.  Brain Lipotoxicity of Phytanic Acid and Very Long-chain Fatty Acids. Harmful Cellular/Mitochondrial Activities in Refsum Disease and X-Linked Adrenoleukodystrophy , 2016, Aging and disease.

[57]  J. Deeney,et al.  Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism. , 2016, Cell reports.

[58]  Gregory Lefebvre,et al.  Medium‐chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte‐neuron lactate and ketone body shuttle systems , 2016, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[59]  J. Berger,et al.  Peroxisomes in brain development and function , 2015, Biochimica et biophysica acta.

[60]  A. Nordenström,et al.  Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency. , 2015, JIMD reports.

[61]  B. Andresen,et al.  Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening. , 2014, Molecular genetics and metabolism.

[62]  R. Valabrègue,et al.  N04 Anaplerotic Therapy Using Triheptanoin Improves Brain Energy Metabolism In Patients With Huntington Disease , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[63]  N. Suzuki,et al.  Roles and Regulation of Ketogenesis in Cultured Astroglia and Neurons Under Hypoxia and Hypoglycemia , 2014, ASN neuro.

[64]  P. Wong,et al.  Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid , 2014, Nature.

[65]  A. Panov,et al.  Fatty Acids in Energy Metabolism of the Central Nervous System , 2014, BioMed research international.

[66]  R. Wanders.  Metabolic functions of peroxisomes in health and disease. , 2014, Biochimie.

[67]  L. Pellerin,et al.  Unraveling the complex metabolic nature of astrocytes , 2013, Front. Cell. Neurosci..

[68]  G. Reiser,et al.  Why does Brain Metabolism not Favor Burning of Fatty Acids to Provide Energy? - Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[69]  E. Nintou,et al.  Cell Survival during Complete Nutrient Deprivation Depends on Lipid Droplet-fueled β-Oxidation of Fatty Acids* , 2013, The Journal of Biological Chemistry.

[70]  Huaxi Xu,et al.  Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy , 2013, Nature Reviews Neurology.

[71]  A. Schousboe,et al.  Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation , 2012, ASN neuro.

[72]  M. Schrader,et al.  The peroxisome: an update on mysteries 2.0 , 2012, Histochemistry and Cell Biology.

[73]  Donald W. Miller,et al.  Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells , 2011, Journal of neurochemistry.

[74]  David J. Begley,et al.  Structure and function of the blood–brain barrier , 2010, Neurobiology of Disease.

[75]  F. LaFerla,et al.  Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood–brain barrier: An in situ cerebral perfusion study , 2009, Neurochemistry International.

[76]  L. Rossetti,et al.  Hypothalamic sensing of fatty acids , 2005, Nature Neuroscience.

[77]  R. Haller,et al.  Energy Contribution of Octanoate to Intact Rat Brain Metabolism Measured by 13C Nuclear Magnetic Resonance Spectroscopy , 2003, The Journal of Neuroscience.

[78]  M. Guzmán,et al.  Is there an astrocyte–neuron ketone body shuttle? , 2001, Trends in Endocrinology & Metabolism.

[79]  M. L. de Ceballos,et al.  The AMP‐Activated Protein Kinase Is Involved in the Regulation of Ketone Body Production by Astrocytes , 1999, Journal of neurochemistry.

[80]  W. Stremmel,et al.  Tissue distribution and cDNA cloning of a human fatty acid transport protein (hsFATP4). , 1998, Biochimica et biophysica acta.

[81]  D. Hardie,et al.  5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? , 1995, European journal of biochemistry.

[82]  H. Hayashi,et al.  Role of peroxisomal fatty acyl-CoA β-oxidation in phospholipid biosynthesis , 1991 .

[83]  F. Amemiya,et al.  Brain and liver pathology in a patient with carnitine deficiency , 1990, Brain and Development.

[84]  R. Wanders,et al.  Zellweger syndrome: Biochemical procedures in diagnosis, prevention and treatment , 1987, Journal of Inherited Metabolic Disease.

[85]  E. Saggerson,et al.  Carnitine acyltransferase activities in rat brain mitochondria. Bimodal distribution, kinetic constants, regulation by malonyl-CoA and developmental pattern. , 1985, The Biochemical journal.

[86]  J. Mead,et al.  Rapid uptake of (I- 14 C) acetate by the adult rat brain 15 seconds after carotid injection. , 1971, Biochimica et biophysica acta.

[87]  G. Dienel.  Brain Glucose Metabolism: Integration of Energetics with Function. , 2019, Physiological reviews.

[88]  R. Dringen,et al.  The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes , 2015, Neurochemical Research.

[89]  Lauren L. Jones,et al.  Acylcarnitines: role in brain. , 2010, Progress in lipid research.

[90]  S. Rapoport,et al.  Cerebral metabolism of plasma [14C]palmitate in awake, adult rat: Subcellular localization , 2004, Neurochemical Research.

[91]  J. de Vellis,et al.  Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture , 1987, Journal of neuroscience research.