Abstract
In recent years, increasing evidence regarding the functional importance of lipid droplets (LDs), cytoplasmic storage organelles in the central nervous system (CNS), has emerged. Although not abundantly present in the CNS under normal conditions in adulthood, LDs accumulate in the CNS during development and aging, as well as in some neurologic disorders. LDs are actively involved in cellular lipid turnover and stress response. By regulating the storage of excess fatty acids, cholesterol, and ceramides in addition to their subsequent release in response to cell needs and/or environmental stressors, LDs are involved in energy production, in the synthesis of membranes and signaling molecules, and in the protection of cells against lipotoxicity and free radicals. Accumulation of LDs in the CNS appears predominantly in neuroglia (astrocytes, microglia, oligodendrocytes, ependymal cells), which provide trophic, metabolic, and immune support to neuronal networks. Here we review the most recent findings on the characteristics and functions of LDs in neuroglia, focusing on astrocytes, the key homeostasis-providing cells in the CNS. We discuss the molecular mechanisms affecting LD turnover in neuroglia under stress and how this may protect neural cell function. We also highlight the role (and potential contribution) of neuroglial LDs in aging and in neurologic disorders.
Highlights
Academic Editors: NatašaThe brain is a highly energy-demanding organ
The molecular mechanisms underlying the reactive oxygen species (ROS)-mediated redistribution of membrane free fatty acids (FFAs) to lipid droplets (LDs) are not yet clear in astrocytes, various studies on other cells implicate the involvement of hypoxia inducible factor 1 (HIF-1) and HIF-2 pathways in astrocytes [141], which can activate the expression of the proteins involved in lipid transport and metabolism, as observed in tumors, myocytes, and other cell types [142,143,144,145]
This review summarizes the most recent research advances on the role of neuroglial
Summary
The brain is a highly energy-demanding organ. representing only 2% of total body mass, it utilizes ~20% of the total O2 consumed by the resting body [1]. Despite not being extensively used to provide energy to the brain, lipids play a crucial role in the maintenance of normal brain function as structural constituents of neuronal and neuroglial cell membranes and precursors of signaling molecules [5]. LDs are dynamic lipid storage organelles in the cell cytoplasm that play a significant role in cellular lipid turnover and stress response [12] by providing substrates for energy metabolism, building blocks for biological membranes, and precursors for signaling molecules in addition to acting as a buffering system against lipotoxicity [13,14]. Alois Alzheimer described “adipose saccules” in brain neuroglial cells of patients with dementia in 1907 [31,32], the role of LDs in central nervous system (CNS) pathology has been greatly overlooked until recently. We highlight the potential contribution of neuroglial and neuronal LDs to aging and neurologic disorders
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