The neuroligins and the synaptic pathway in Autism Spectrum Disorder
Authors/Creators
- 1. Dept. Biology and Biotechnology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
- 2. Lab. Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy; Dept. Systems Medicine, University Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
- 3. Lab. "Architecture et Fonction des Macromol´ecules Biologiques", CNRS/Aix Marseille Univ, Facult´e des Sciences - Campus Luminy, 163 Avenue de Luminy, 13288 Marseille cedex 09, France
- 4. Lab. Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy
Description
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.
Files
Restricted
The record is publicly accessible, but files are restricted. Log in to check if you have access.
Request access
If you would like to request access to these files, please fill out the form below.
You need to satisfy these conditions in order for this request to be accepted:
The manuscript file can be shared privately to individual researchers requesting it for their personal use by email to p.bonsi@hsantalucia.it
Free access to the manuscript will be granted from March 28 2022.
You are currently not logged in. Do you have an account? Log in here