Astrocyte metabolism and signaling pathways in the CNS

Abstract

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

Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases

“…Sphingosine kinase is the enzyme responsible for producing sphingosine-1-phosphate (sph-1-P) in response to various stimuli, such as growth factors, cytokines, and agonists of GPCRs [ 42 ]. A number of studies suggest that sphingolipid signaling can be a promising novel target for neuroprotection, aiming to counteract the pathophysiology of CNS disorders related to oxidative stress, mitochondrial dysfunction, cell apoptosis, and lipid hydrolysis [ 43 , 44 ]. Sph-1-P is the primary regulatory lipid involved in PLD metabolism and has been implicated in the regulation of various aspects of cell physiology, such as mitogenesis, differentiation, migration, and apoptosis [ 45 , 46 ].…”

Primary Astrocytes Purification and Immortalization

“…Astrocytes, the most abundant type of glial cells in the central nervous system (CNS), account for 20% to 50% of total cells in the CNS depending on the studied species (Hasel & Liddelow, 2021). Astrocytes play dual roles in neuronal development, network formation, and overall CNS homeostasis (Lee et al., 2022): astrocytes contribute to neuronal branching, synapse formation, and the maturation of neuronal circuits during neurogenesis (Zhang et al., 2023); and reactive astrocytes induced by CNS injury and diseases lose their supportive functions and induce neuronal and oligodendrocyte death (Sofroniew, 2020). Moreover, abnormalities in astrocytic functions are tightly associated with the pathogenesis of many neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) (Qian et al., 2023).…”