Ricerc@Sapienza

Graves’ disease (GD) is an autoimmune chronic thyroiditis frequently associated with development of Graves’ orbitopathy (GO) characterized by proptosis, strabismus, impairment of visual function, ocular surface inflammation and dry eye. As consequence, patients with GO experience impairment of quality of life and social function and could develop a neurobehavioral syndrome, ranging from anxious to depressive or psychotic disorders. To date, the pathogenic mechanism underlying neuropsychiatric disorders in patients with GD has not been clearly understood.

4-hydroxy-2-nonenal (HNE) is considered to be a strong marker of oxidative stress; the interaction between HNE and cellular proteins leads to the formation of HNE-protein adducts able to alter cellular homeostasis and cause the development of a pathological state. By virtue of its high lipid concentration, oxygen utilization, and the presence of metal ions participating to redox reactions, the brain is highly susceptible to the formation of free radicals and HNE-related compounds. A variety of neuropsychiatric disorders have been associated with elevations of HNE concentration.

The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies