TY - JOUR
T1 - Glutaminase in microglia
T2 - A novel regulator of neuroinflammation
AU - Ding, Lu
AU - Xu, Xiaonan
AU - Li, Congcong
AU - Wang, Yi
AU - Xia, Xiaohuan
AU - Zheng, Jialin C.
N1 - Funding Information:
This work was supported in part by research grants from the Major Research plan of the National Natural Science Foundation of China (No. 91949204 to JCZ), the State Key Program of the National Natural Science Foundation of China (No. 81830037 to JCZ), the National Basic Research Program of China (973 Program Grant No. 2014CB965001 to JCZ), the National Institutes of Health (1R01NS097195-01 to JCZ), the National Natural Science Foundation of China (No. 81901333 to XX), Shanghai Sailing Program (No. 19YF1451700 to XX), and National Natural Science Foundation of China (No. 81801063 to YW).
Funding Information:
This work was supported in part by research grants from the Major Research plan of the National Natural Science Foundation of China (No. 91949204 to JCZ), the State Key Program of the National Natural Science Foundation of China (No. 81830037 to JCZ), the National Basic Research Program of China (973 Program Grant No. 2014CB965001 to JCZ), the National Institutes of Health ( 1R01NS097195-01 to JCZ), the National Natural Science Foundation of China (No. 81901333 to XX), Shanghai Sailing Program (No. 19YF1451700 to XX), and National Natural Science Foundation of China (No. 81801063 to YW).
Publisher Copyright:
© 2020 The Author(s)
PY - 2021/2
Y1 - 2021/2
N2 - Neuroinflammation is the inflammatory responses that are involved in the pathogenesis of most neurological disorders. Glutaminase (GLS) is the enzyme that catalyzes the hydrolysis of glutamine to produce glutamate. Besides its well-known role in cellular metabolism and excitatory neurotransmission, GLS has recently been increasingly noticed to be up-regulated in activated microglia under pathological conditions. Furthermore, GLS overexpression induces microglial activation, extracellular vesicle secretion, and neuroinflammatory microenvironment formation, which, are compromised by GLS inhibitors in vitro and in vivo. These results indicate that GLS has more complicated implications in brain disease etiology than what are previously known. In this review, we introduce GLS isoforms, expression patterns in the body and the brain, and expression/activities regulation. Next, we discuss the metabolic and neurotransmission functions of GLS. Afterwards, we summarize recent findings of GLS-mediated microglial activation and pro-inflammatory extracellular vesicle secretion, which, in turns, induces neuroinflammation. Lastly, we provide a comprehensive discussion for the involvement of microglial GLS in the pathogenesis of various neurological disorders, indicating microglial GLS as a promising target to treat these diseases.
AB - Neuroinflammation is the inflammatory responses that are involved in the pathogenesis of most neurological disorders. Glutaminase (GLS) is the enzyme that catalyzes the hydrolysis of glutamine to produce glutamate. Besides its well-known role in cellular metabolism and excitatory neurotransmission, GLS has recently been increasingly noticed to be up-regulated in activated microglia under pathological conditions. Furthermore, GLS overexpression induces microglial activation, extracellular vesicle secretion, and neuroinflammatory microenvironment formation, which, are compromised by GLS inhibitors in vitro and in vivo. These results indicate that GLS has more complicated implications in brain disease etiology than what are previously known. In this review, we introduce GLS isoforms, expression patterns in the body and the brain, and expression/activities regulation. Next, we discuss the metabolic and neurotransmission functions of GLS. Afterwards, we summarize recent findings of GLS-mediated microglial activation and pro-inflammatory extracellular vesicle secretion, which, in turns, induces neuroinflammation. Lastly, we provide a comprehensive discussion for the involvement of microglial GLS in the pathogenesis of various neurological disorders, indicating microglial GLS as a promising target to treat these diseases.
KW - Cellular metabolism
KW - Extracellular vesicle
KW - Microglia
KW - Neuroinflammation
KW - Neurological disorder
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U2 - 10.1016/j.bbi.2020.11.038
DO - 10.1016/j.bbi.2020.11.038
M3 - Article
C2 - 33278560
AN - SCOPUS:85097745985
SN - 0889-1591
VL - 92
SP - 139
EP - 156
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -