Therapy-refractory schizophrenia in a patient who previously suffered from Meige's syndrome.

The main symptoms of Meige's syndrome are involuntary eye blinking with muddled speech and uncontrollable contraction of the platysma muscle characterized by segmental, primarily oromandibular, dystonia (hyperkinesia). It can also develop after long-term medication of first- and second-generation antipsychotics. Here, we report the case of a Japanese female schizophrenic patient comorbid with Meige's syndrome and hyperthyroidism. We discuss the relationship between the three diseases, that is, schizophrenia, Meige's syndrome, and hyperthyroidism. Our intention is to consider the important role of the cerebral basal ganglia, where little attention has been given in regard to schizophrenia and Meige's syndrome. A part of this article was presented in a poster section at the joint congress of the 28th Annual Meeting of the Japanese Society of Clinical Neuropsychopharmacology and the 48th Annual Meeting of the Japanese Society of Neuropsychopharmacology held in 2018.

Dual role of the carboxyl-terminal region of pig liver L-kynurenine 3-monooxygenase: mitochondrial-targeting signal and enzymatic activity.

l-kynurenine 3-monooxygenase (KMO) is an NAD(P)H-dependent flavin monooxygenase that catalyses the hydroxylation of l-kynurenine to 3-hydroxykynurenine, and is localized as an oligomer in the mitochondrial outer membrane. In the human brain, KMO may play an important role in the formation of two neurotoxins, 3-hydroxykynurenine and quinolinic acid, both of which provoke severe neurodegenerative diseases. In mosquitos, it plays a role in the formation both of eye pigment and of an exflagellation-inducing factor (xanthurenic acid). Here, we present evidence that the C-terminal region of pig liver KMO plays a dual role. First, it is required for the enzymatic activity. Second, it functions as a mitochondrial targeting signal as seen in monoamine oxidase B (MAO B) or outer membrane cytochrome b(5). The first role was shown by the comparison of the enzymatic activity of two mutants (C-terminally FLAG-tagged KMO and carboxyl-terminal truncation form, KMOΔC50) with that of the wild-type enzyme expressed in COS-7 cells. The second role was demonstrated with fluorescence microscopy by the comparison of the intracellular localization of the wild-type, three carboxyl-terminal truncated forms (ΔC20, ΔC30 and ΔC50), C-terminally FLAG-tagged wild-type and a mutant KMO, where two arginine residues, Arg461-Arg462, were replaced with Ser residues.