Our research focuses on understanding the physiological and pathophysiological role of thyroid hormones (T4 or thyroxine and T3 or 3,5,3'-triiodothyronine) action in the central nervous system (CNS), both during development and at adult stages. We are especially interested in the identification of structural and functional alterations in the CNS due to defects in thyroid hormone availability and/or signaling. All this in order to understand disease mechanisms and characterize biomarkers to develop therapeutic strategies in preclinical studies.
To achieve this goal, we analyze the phenotype of disease animal models deficient in proteins involved in the metabolism and plasma-membrane transport of thyroid hormones. We use different experimental approaches performing in vivo studies to characterize biochemical, histological, behavioral and cognitive alterations as a consequence of impaired availability or signaling of thyroid hormones in the CNS in several diseases.
We also analyze the histopathology of human autopsy brain tissues from Allan-Herndon-Dudley syndrome patients. This syndrome is an ultrarare disease due to inactivating mutations in the monocarboxylate transporter 8 (MCT8; SLC16A2 gene), an important thyroid hormone transporter in the brain barriers and the plasma membrane of neural cells. MCT8 presents the highest specificity for the transport of thyroid hormones among all the transmembrane proteins that can transport these hormones.
Nowadays there are no effective treatments for the severe neurological alterations of Allan-Herndon-Dudley Syndrome patients. For this reason, we are also actively working, thorough preclinical research using disease animal models, to repair/palliate the deficiency of the specific thyroid hormone transporter MCT8 in the CNS, testing different pharmacological therapies and different routes of drug delivery to the brain to bypass the brain barriers.
Our studies will shed light on the pathophysiology and on the CNS disease mechanisms associated to defects in thyroid hormone signaling and will even contribute to the development of new therapeutic strategies. These studies will also help to better understand the important role of thyroid hormones in brain activity and plasticity.