Benutzerspezifische Werkzeuge

Project 6

Involvement of ALADIN in adrenal cell function and hormone response

The triple A syndrome is an autosomal recessive disorder, which is characterized by the clinical triad of adrenal insufficiency, alacrima and achalasia of the cardia. Patients present with glucocorticoid deficiency and in some cases with mineralocorticoid and adrenal androgen deficiencies. A severe dysautonomia points to an impaired function of sympathetic and parasympathetic nerves and to a lack of catecholamine secretion by adrenomedullary chromaffin cells. The syndrome is caused by mutations in the AAAS gene encoding ALADIN, a protein of the nuclear pore complex (NPC).

We will investigate mechanisms by which ALADIN protects the adrenal cells from reactive oxygen species and will test the potential of antioxidative treatment. After proof of principle in cell culture and our mouse models we prospectively plan a multicenter clinical trial in our world-largest cohort of triple A syndrome patients.