A disintegrine and metalloproteinase 10 (ADAM10), a member of the large ADAM transmembrane protein family, is expressed at high levels in the brain and regulates the molecular organization and
activity of the excitatory synapse by shedding postsynaptic proteins.impairments in
ADAM10 level and/or activity are detrimental for the human brain. ADAM10 has been linked to epilepsy, Alzheimer’s disease (AD), and the developmental disorder Fragile X syndrome.

In a collaborative study with Chira Zuccato (University of Milan, Italy) it was demonstrated that the hyperactivity of ADAM10 and its associated increased proteolysis of its synaptic substrate N-cadherin are decisive neurotoxic events in the synaptic and cognitive decline typically found in Huntington Disease. Huntington’s diseaseis an autosomal dominant neurodegenerative disorder caused by a polyglutamine (polyQ) expansion in the huntingtin (HTT) protein.

Suggested reading:

Vezzoli, E., Caron, I., Talpo, F., Besusso, D., Conforti, P., Battaglia, E., Sogne, E., Falqui, A.,Petricca, L., Verani, M., Martufi, P., Caricasole, A., Bresciani, A.,Cecchetti, O., Rivetti di Val Cervo, P., Sancini, G., Riess, O., Nguyen, H., Seipold, L., Saftig, P., Biella, G., Cattaneo, E., Zuccato, C. (2019)
Inhibiting pathologically active ADAM10 rescues synaptic and cognitive decline in Huntington’s disease.
J. Clin. Invest., in press