The Gut-Brain Axis in Autism Spectrum Disorder: A Focus on the Metalloproteases ADAM10 and ADAM17

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-12, Vol.22 (1), p.118
Main Authors: Zheng, Yuanpeng, Verhoeff, Tessa A, Perez Pardo, Paula, Garssen, Johan, Kraneveld, Aletta D
Format: Article
Language:English
Subjects:
A Disintegrin And Metalloprotease (ADAM)
ADAM10
Autism
Autism Spectrum Disorder (ASD)
Binding sites
Cell adhesion & migration
Chemokines
Digestive system
Enzymes
gut-brain axis
Homeostasis
Inflammation
Intestine
metalloproteases
Microbiota
Nervous system
neuroinflammation
Pathogenesis
Peptides
Permeability
Proteins
Review
Social behavior
Social factors
Sperm
Synapses
Synaptogenesis
Tumor necrosis factor-TNF
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Summary:Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intestines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, homeostasis and inflammation. These metalloproteases might be involved in microbiota-gut-brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut-brain axis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22010118