TY - JOUR
T1 - The neuroligins and the synaptic pathway in Autism Spectrum Disorder
AU - Trobiani, Laura
AU - Meringolo, Maria
AU - Diamanti, Tamara
AU - Bourne, Yves
AU - Marchot, Pascale
AU - Martella, Giuseppina
AU - Dini, Luciana
AU - Pisani, Antonio
AU - De Jaco, Antonella
AU - Bonsi, Paola
N1 - Funding Information:
This work was partially supported by the Italian Ministry of Health, Ricerca Corrente 2020 (PB), and Sapienza University of Rome 2019 (ADJ). The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the review; and in the decision to submit the article for publication.
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - The genetics underlying autism spectrum disorder (ASD) is complex and heterogeneous, and de novo variants are found in genes converging in functional biological processes. Neuronal communication, including trans-synaptic signaling involving two families of cell-adhesion proteins, the presynaptic neurexins and the postsynaptic neuroligins, is one of the most recurrently affected pathways in ASD. Given the role of these proteins in determining synaptic function, abnormal synaptic plasticity and failure to establish proper synaptic contacts might represent mechanisms underlying risk of ASD. More than 30 mutations have been found in the neuroligin genes. Most of the resulting residue substitutions map in the extracellular, cholinesterase-like domain of the protein, and impair protein folding and trafficking. Conversely, the stalk and intracellular domains are less affected. Accordingly, several genetic animal models of ASD have been generated, showing behavioral and synaptic alterations. The aim of this review is to discuss the current knowledge on ASD-linked mutations in the neuroligin proteins and their effect on synaptic function, in various brain areas and circuits.
AB - The genetics underlying autism spectrum disorder (ASD) is complex and heterogeneous, and de novo variants are found in genes converging in functional biological processes. Neuronal communication, including trans-synaptic signaling involving two families of cell-adhesion proteins, the presynaptic neurexins and the postsynaptic neuroligins, is one of the most recurrently affected pathways in ASD. Given the role of these proteins in determining synaptic function, abnormal synaptic plasticity and failure to establish proper synaptic contacts might represent mechanisms underlying risk of ASD. More than 30 mutations have been found in the neuroligin genes. Most of the resulting residue substitutions map in the extracellular, cholinesterase-like domain of the protein, and impair protein folding and trafficking. Conversely, the stalk and intracellular domains are less affected. Accordingly, several genetic animal models of ASD have been generated, showing behavioral and synaptic alterations. The aim of this review is to discuss the current knowledge on ASD-linked mutations in the neuroligin proteins and their effect on synaptic function, in various brain areas and circuits.
KW - Animal model
KW - Behaviour
KW - Endoplasmic reticulum
KW - excitatory/inhibitory balance
KW - Genetics
KW - Homeostatic mechanisms
KW - Misfolding
KW - Physiology
KW - Synaptic plasticity
KW - Trafficking
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=85092220684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092220684&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2020.09.017
DO - 10.1016/j.neubiorev.2020.09.017
M3 - Review article
C2 - 32991906
AN - SCOPUS:85092220684
VL - 119
SP - 37
EP - 51
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
SN - 0149-7634
ER -