PMID- 30916550
OWN - NLM
STAT- MEDLINE
DCOM- 20200521
LR  - 20200521
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 10
IP  - 5
DP  - 2019 May 15
TI  - Autoimmune Attack of the Neuromuscular Junction in Myasthenia Gravis: Nicotinic 
      Acetylcholine Receptors and Other Targets.
PG  - 2186-2194
LID - 10.1021/acschemneuro.9b00041 [doi]
AB  - The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the 
      pentameric ligand-gated ion channels, is ubiquitously distributed in the central 
      and peripheral nervous systems, and its members are the targets for both genetic 
      and acquired forms of neurological disorders. In the central nervous system, 
      nAChRs contribute to the pathological mechanisms of neurodegenerative disorders, 
      such as Alzheimer and Parkinson diseases. In the peripheral nerve-muscle synapse, 
      the vertebrate neuromuscular junction, "classical" myasthenia gravis (MG) and 
      other forms of neuromuscular transmission disorders are antibody-mediated 
      autoimmune diseases. In MG, antibodies to the nAChR bind to the postsynaptic 
      receptors and activate the classical complement pathway culminating in the 
      formation of the membrane attack complex, with the subsequent destruction of the 
      postsynaptic apparatus. Divalent nAChR-antibodies also cause internalization and 
      loss of the nAChRs. Loss of receptors by either mechanism results in the muscle 
      weakness and fatigability that typify the clinical manifestations of the disease. 
      Other targets for antibodies, in a minority of patients, include muscle specific 
      kinase (MuSK) and low-density lipoprotein related protein 4 (LRP4). This brief 
      Review analyzes the current status of muscle-type nAChR in relation to the 
      pathogenesis of autoimmune diseases affecting the peripheral cholinergic synapse.
FAU - Paz, Mariela L
AU  - Paz ML
AD  - Immunology Department, Faculty of Pharmacy and Biochemistry, IDEHU-CONICET , 
      University of Buenos Aires , Junin 956 , C1113AAD Buenos Aires , Argentina.
FAU - Barrantes, Francisco J
AU  - Barrantes FJ
AUID- ORCID: 0000-0002-4745-681X
AD  - Laboratory of Molecular Neurobiology, Biomedical Research Institute (BIOMED) , 
      UCA-CONICET , Av. Alicia Moreau de Justo 1600 , C1107AFF Buenos Aires , 
      Argentina.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190412
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Autoantibodies)
RN  - 0 (Receptors, Nicotinic)
SB  - IM
MH  - Animals
MH  - Autoantibodies/*immunology
MH  - Humans
MH  - Myasthenia Gravis/*immunology
MH  - Neuromuscular Junction/*immunology
MH  - Receptors, Nicotinic/*immunology
MH  - Synaptic Transmission/immunology
OTO - NOTNLM
OT  - Myasthenia gravis
OT  - antireceptor antibody
OT  - autoimmune diseases
OT  - end plate
OT  - neuromuscular junction
OT  - nicotinic acetylcholine receptor
EDAT- 2019/03/28 06:00
MHDA- 2020/05/22 06:00
CRDT- 2019/03/28 06:00
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2020/05/22 06:00 [medline]
PHST- 2019/03/28 06:00 [entrez]
AID - 10.1021/acschemneuro.9b00041 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2019 May 15;10(5):2186-2194. doi: 
      10.1021/acschemneuro.9b00041. Epub 2019 Apr 12.