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Expert Opin Ther Targets. 2017 Nov;21(11):1017-1026. doi: 10.1080/14728222.2017.1386176. Epub 2017 Oct 3.

ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer's disease.

Author information

1
a Department of Pharmacological and Biomolecular Sciences , Università degli Studi di Milano , Milan , Italy.
2
b Neurology Unit, Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences , University of Brescia , Brescia , Italy.
3
c Department of Neurosciences, Psychology, Drug Research, and Child Health , University of Florence , Florence , Italy.

Abstract

In the central nervous system a disintegrin and metalloproteinase 10 (ADAM10) controls several functions such as neurodevelopment, synaptic plasticity and dendritic spine morphology thanks to its activity towards a high number of substrates, including the synaptic cell adhesion molecules as the Amyloid Precursor Protein, N-cadherin, Notch and Ephrins. In particular, ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse. Consequently, an alteration of ADAM10 activity is strictly correlated to the onset of different types of synaptopathies, ranging from neurodevelopmental disorders, i.e. autism spectrum disorders, to neurodegenerative diseases, i.e. Alzheimer's Disease. Areas covered: We describe the most recent discoveries in understanding of the role of ADAM10 activity at the glutamatergic excitatory synapse and its involvement in the onset of neurodevelopmental and neurodegenerative disorders. Expert opinion: A progress in the understanding of the molecular mechanisms driving ADAM10 activity at synapses and its alterations in brain disorders is the first step before designing a specific drug able to modulate ADAM10 activity.

KEYWORDS:

Autism spectrum disorders; neurodegeneration; synapse; trafficking

PMID:
28960088
DOI:
10.1080/14728222.2017.1386176
[Indexed for MEDLINE]

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