First-in-class thyrotropin-releasing hormone (TRH)-based compound binds to a pharmacologically distinct TRH receptor subtype in human brain and is effective in neurodegenerative models.

JAK4D, a first-in-class thyrotropin-releasing hormone (TRH)-based compound, is a prospective therapeutic candidate offering a multifaceted approach to treating neurodegeneration and other CNS conditions. The purpose of these studies was to determine the ability of JAK4D to bind to TRH receptors in human brain and to evaluate its neuropharmacological effects in neurodegenerative animal models. Additionally, JAK4D brain permeation was examined in mouse, and initial toxicology was assessed in vivo and in vitro.

Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype.

The chromosome 17q21.31 deletion syndrome is a genomic disorder characterized by highly distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior. Here, we show that de novo loss-of-function mutations in KANSL1 (also called KIAA1267) cause a full del(17q21.

Highly reactive oxygen species: detection, formation, and possible functions.

The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen.

Migraine-like headache and status migrainosus as attacks of multiple sclerosis in a child.

The incidence of headache at the onset of relapsing-remitting pediatric multiple sclerosis (MS) is more frequent than in the adult MS population, but headache as the only symptom of a relapse, both in adults and children, is unusual. Here we describe the case of a 5-year-old child who developed MS and in whom migraine-like headache was the presenting symptom at both the onset of the disease and the following 2 relapses. Moreover, the first relapse was characterized by the occurrence of headache that fulfilled the time criteria for status migrainosus.