PMID- 36033606
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220830
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 16
DP  - 2022
TI  - EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic 
      review.
PG  - 952096
LID - 10.3389/fnins.2022.952096 [doi]
LID - 952096
AB  - Glutamate is the main excitatory neurotransmitter in the human central nervous 
      system, responsible for a wide variety of normal physiological processes. 
      Glutamatergic metabolism and its sequestration are tightly regulated in the 
      normal human brain, and it has been demonstrated that dysregulation of the 
      glutamatergic system can have wide-ranging effects both in acute brain injury and 
      neurodegenerative diseases. The excitatory amino acid transporter 2 (EAAT2) is 
      the dominant glutamatergic transporter in the human brain, responsible for 
      efficient removal of glutamate from the synaptic cleft for recycling within glial 
      cells. As such, it has a key role in maintaining excitatory-inhibitory 
      homeostasis. Animal studies have demonstrated dysregulation or alterations of 
      EAAT2 expression can have implications in neurodegenerative disorders. Despite 
      extensive research into glutamatergic alterations in AD mouse models, there is a 
      lack of studies examining the expression of EAAT2 within the AD human brain. In 
      this systematic review, 29 articles were identified that either analyzed EAAT2 
      expression in the AD human brain or used a human-derived cell culture. Studies 
      were inconclusive as to whether EAAT2 was upregulated or downregulated in AD. 
      However, changes in localization and correlation between EAAT2 expression and 
      symptomatology was noted. These findings implicate EAAT2 alterations as a key 
      process in AD progression and highlight the need for further research into the 
      characterization of EAAT2 processes in normal physiology and disease in human 
      tissue and to identify compounds that can act as EAAT2 neuromodulators.
CI  - Copyright (c) 2022 Wood, Yeung, Faull and Kwakowsky.
FAU - Wood, Oliver W G
AU  - Wood OWG
AD  - Department of Anatomy and Medical Imaging, Faculty of Medical and Health 
      Sciences, Centre for Brain Research, University of Auckland, Auckland, New 
      Zealand.
FAU - Yeung, Jason H Y
AU  - Yeung JHY
AD  - Department of Anatomy and Medical Imaging, Faculty of Medical and Health 
      Sciences, Centre for Brain Research, University of Auckland, Auckland, New 
      Zealand.
FAU - Faull, Richard L M
AU  - Faull RLM
AD  - Department of Anatomy and Medical Imaging, Faculty of Medical and Health 
      Sciences, Centre for Brain Research, University of Auckland, Auckland, New 
      Zealand.
FAU - Kwakowsky, Andrea
AU  - Kwakowsky A
AD  - Department of Anatomy and Medical Imaging, Faculty of Medical and Health 
      Sciences, Centre for Brain Research, University of Auckland, Auckland, New 
      Zealand.
AD  - Pharmacology and Therapeutics, Galway Neuroscience Centre, School of Medicine, 
      Ollscoil na Gaillimhe - University of Galway, Galway, Ireland.
LA  - eng
PT  - Systematic Review
DEP - 20220810
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC9399514
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - EAAT2
OT  - glutamate transporter
OT  - hippocampus
OT  - human brain
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/30 06:00
MHDA- 2022/08/30 06:01
PMCR- 2022/01/01
CRDT- 2022/08/29 04:56
PHST- 2022/05/24 00:00 [received]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2022/08/29 04:56 [entrez]
PHST- 2022/08/30 06:00 [pubmed]
PHST- 2022/08/30 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2022.952096 [doi]
PST - epublish
SO  - Front Neurosci. 2022 Aug 10;16:952096. doi: 10.3389/fnins.2022.952096. 
      eCollection 2022.