Mercury neurotoxicity.
© 2011 http://idw-online.de
Mercury is a direct and potent gamma-secretase inhibitor affecting Notch processing and development in Drosophila.
Mercury is a major cause of neurodevelopmental disorders as observed following contaminations in several parts of the world. Prenatal exposure to mercury leads to serious neurological pathologies in infants, such as cerebral palsy, seizures, microcephaly and mental retardation. The molecular interactions leading to mercury toxicity remain largely unknown. Using a combination of in vitro and in vivo approaches, the team of Prof. PC. Fraering (CMSN), in collaboration with the team of Prof. B. Lemaitre (UPLEM), discovered that mercury is a direct and potent inhibitor of gamma-secretase, a key enzyme complex involved in the Notch developmental pathway and Alzheimer’s disease. These findings suggest that inhibition of gamma-secretase and disruption of the Notch developmental pathway participate to the mercury-induced toxicity in the nervous system (and show that mercury-chelating compounds used clinically for mercury detoxification reverse this process).