Lipid Droplets in Neurodegenerative Disorders

Frontiers in Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Июль 29, 2020

Lipid droplets have been long regarded as simple storage depots of intracellular neutral lipid. However, recent studies informed significant roles for lipid in cellular signaling, metabolic disease, pathophysiology, and inflammation. While droplet biology has well-explored the periphery, within brain are relatively understudied. The presence function these dynamic organelles central nervous system recently gained much more attention, especially context neurodegeneration. In this review, we seek to summarize current understanding brain, with an emphasis on their relevance neurodegenerative diseases. We hope update investigators effort open new avenues investigation into under-appreciated organelle.

Язык: Английский

---

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

FEBS Journal, Год журнала: 2022, Номер 290(6), С. 1420 - 1453

Опубликована: Янв. 8, 2022

Alzheimer’s disease (AD) is an age‐associated neurodegenerative disorder with multifactorial etiology, intersecting genetic and environmental risk factors, a lack of disease‐modifying therapeutics. While the abnormal accumulation lipids was described in very first report AD neuropathology, it not until recent decades that lipid dyshomeostasis became focus research. Clinically, lipidomic metabolomic studies have consistently shown alterations levels various classes emerging early stages brains. Mechanistically, discovery research revealed multifaceted interactions between metabolism key pathogenic mechanisms including amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, myelin degeneration. In present review, converging evidence defining summarized, followed by discussions on which contributes to pathogenesis modifies risk. Furthermore, lipid‐targeting therapeutic strategies, modification their efficacy stage, ApoE status, metabolic vascular profiles, are reviewed.

Язык: Английский

---

Triacylglycerol Metabolism in Drosophila melanogaster

Genetics, Год журнала: 2018, Номер 210(4), С. 1163 - 1184

Опубликована: Дек. 1, 2018

Abstract Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition its evolutionarily conserved importance as an source, TAG turnover crucial metabolism of structural and signaling lipids. These neutral lipids are also key players development disease. Here, we review Drosophila model system. Recently, fruit fly has attracted renewed attention research due unique experimental approaches it affords studying tissue-autonomous interorgan regulation lipid vivo. Following overview systemic control body fat stores, will cover anabolic, enzymatic, regulatory processes, which begin dietary breakdown de novo lipogenesis that results droplet storage. Next, focus on lipolytic mobilize storage make metabolically accessible either or a building block for biosynthesis other classes. Since buildup involves various organs, highlight avenues transport, at heart functional integration organismic metabolism. Finally, draw some “missing links” basic conclude perspective how can be exploited study metabolic roles diverse

Язык: Английский

---

Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives

Frontiers in Physiology, Год журнала: 2022, Номер 12

Опубликована: Янв. 11, 2022

Astrocytes play key roles in the regulation of brain energy metabolism, which has a major impact on functions, including memory, neuroprotection, resistance to oxidative stress and homeostatic tone. Energy demands are very large, as they continuously account for 20-25% whole body's consumption. supply is tightly linked neuronal activity, providing origin signals detected by widely used functional imaging techniques such magnetic resonance positron emission tomography. In particular, neuroenergetic coupling regulated astrocytes through glutamate uptake that triggers astrocytic aerobic glycolysis leads glucose lactate release, mechanism known Astrocyte Neuron Lactate Shuttle. Other neurotransmitters noradrenaline Vasoactive Intestinal Peptide mobilize glycogen, reserve exclusively localized astrocytes, also resulting release. then transferred neurons where it used, after conversion pyruvate, rapid substrate, signal modulates excitability, homeostasis, expression survival plasticity genes. Importantly, more generally cerebral metabolism progressively deteriorate aging age-associated neurodegenerative diseases Alzheimer's disease. This decreased actually represents common feature several neurological pathologies. Here, we review critical role how dysregulation astrocyte-mediated metabolic pathways involved hypometabolism. Further, summarize recent efforts at preclinical clinical stages target hypometabolism development new therapeutic interventions age-related diseases.

Язык: Английский

---

Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects

Frontiers in Aging Neuroscience, Год журнала: 2021, Номер 13

Опубликована: Июнь 24, 2021

While the central nervous system compromises 2% of our body weight, it harbors up to 25% body's cholesterol. Cholesterol levels in brain are tightly regulated for physiological function, but mounting evidence indicates that excessive cholesterol accumulates Alzheimer's disease (AD), where may drive AD-associated pathological changes. This seems especially relevant late-onset AD, as several major genetic risk factors functionally associated with metabolism. In this review we discuss different systems maintain metabolism healthy brain, and how dysregulation these processes can lead, or contribute to, disease. We will also AD-risk genes might impact downstream AD pathology. Finally, address outstanding questions field recent technical advances CRISPR/Cas9-gene editing induced pluripotent stem cell (iPSC)-technology aid study problems.

Язык: Английский

---