PMID- 31031597
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 13
DP  - 2019
TI  - Role of Glutamatergic Excitotoxicity in Neuromyelitis Optica Spectrum Disorders.
PG  - 142
LID - 10.3389/fncel.2019.00142 [doi]
LID - 142
AB  - Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder 
      mediated by immune-humoral responses directed against central nervous system 
      (CNS) antigens. Most patients are positive for specific immunoglobulin G (IgG) 
      auto-antibodies for aquaporin-4 (AQP4), a water channel present in astrocytes. 
      Antigen-antibody binding promotes complement system cascade activation, immune 
      system cell infiltration, IgG deposition, loss of AQP4 and excitatory amino acid 
      transporter 2 (EAAT2) expression on the astrocytic plasma membrane, triggering 
      necrotic destruction of spinal cord tissue and optic nerves. Astrocytes are very 
      important cells in the CNS and, in addition to supporting other nerve cells, they 
      also regulate cerebral homeostasis and control glutamatergic synapses by 
      modulating neurotransmission in the cleft through the high-affinity glutamate 
      transporters present in their cell membrane. Specific IgG binding to AQP4 in 
      astrocytes blocks protein functions and reduces EAAT2 activity. Once compromised, 
      EAAT2 cannot take up free glutamate from the extracellular space, triggering 
      excitotoxicity in the cells, which is characterized by overactivation of 
      glutamate receptors in postsynaptic neurons. Therefore, the longitudinally 
      extensive myelitis and optic neuritis lesions observed in patients with NMOSD may 
      be the result of primary astrocytic damage triggered by IgG binding to AQP4, 
      which can activate the immune-system cascade and, in addition, downregulate 
      EAAT2. All these processes may explain the destructive lesions in NMOSD secondary 
      to neuroinflammation and glutamatergic excitotoxicity. New or repurposed existing 
      drugs capable of controlling glutamatergic excitotoxicity may provide new 
      therapeutic options to reduce tissue damage and permanent disability after NMOSD 
      attacks.
FAU - da Silva, Ana Paula Bornes
AU  - da Silva APB
AD  - Molecular and Cellular Biology Laboratory, Brain Institute, Pontifical Catholic 
      University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
AD  - Medical School, Institute of Geriatrics and Gerontology, Graduate Program in 
      Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul 
      (PUCRS), Porto Alegre, Brazil.
FAU - Souza, Debora Guerini
AU  - Souza DG
AD  - Graduate Program in Biological Sciences: Biochemistry, Federal University of Rio 
      Grande do Sul (UFRGS), Porto Alegre, Brazil.
FAU - Souza, Diogo Onofre
AU  - Souza DO
AD  - Graduate Program in Biological Sciences: Biochemistry, Federal University of Rio 
      Grande do Sul (UFRGS), Porto Alegre, Brazil.
FAU - Machado, Denise Cantarelli
AU  - Machado DC
AD  - Molecular and Cellular Biology Laboratory, Brain Institute, Pontifical Catholic 
      University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
AD  - Medical School, Institute of Geriatrics and Gerontology, Graduate Program in 
      Biomedical Gerontology, Pontifical Catholic University of Rio Grande do Sul 
      (PUCRS), Porto Alegre, Brazil.
FAU - Sato, Douglas Kazutoshi
AU  - Sato DK
AD  - Molecular and Cellular Biology Laboratory, Brain Institute, Pontifical Catholic 
      University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190412
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6473164
OTO - NOTNLM
OT  - antibody
OT  - aquaporin-4
OT  - astrocytes
OT  - excitotoxicity
OT  - glutamate
OT  - neuromyelitis optica spectrum disorders
EDAT- 2019/04/30 06:00
MHDA- 2019/04/30 06:01
PMCR- 2019/01/01
CRDT- 2019/04/30 06:00
PHST- 2018/12/17 00:00 [received]
PHST- 2019/03/21 00:00 [accepted]
PHST- 2019/04/30 06:00 [entrez]
PHST- 2019/04/30 06:00 [pubmed]
PHST- 2019/04/30 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2019.00142 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2019 Apr 12;13:142. doi: 10.3389/fncel.2019.00142. 
      eCollection 2019.