Only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. Public education concerning headaches is one of the most urgent issues in Japan.

Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells. We identi¢ed phosphatidylinositol 3-kinase (PI3K) and Nrf2 as important molecules in the induction of heme oxygenase-1, thioredoxin, and peroxiredoxin-I. PI3K-related signal controlled Nrf2 activation, and consequently, PI3K inhibitors blocked the nuclear translocation of Nrf2 and induction of stress proteins. These observations suggest that PI3K and Nrf2 are key molecules in maintaining suitable conditions under oxidative stress and ferrous metabolism.

The vestibulospinal system was evaluated using a stabilometric method in patients with migraine and episodic tension-type headache during headache-free periods. Migraine patients often complain of dizziness or vertigo during headache attacks and some exhibit these symptoms between attacks. Computerized static stabilometry is a reliable and non-invasive technique to evaluate the equilibrium function in various diseases. The subjects consisted of 21 patients with migraine, 12 patients with episodic tension-type headache and, age-and sex-matched controls. We performed two sets of static stabilometric measurements with eyes open (EO) and eyes closed (EC) for 30 s. The averages of two sessions of the following six stabilometric parameters were used for the analysis: locus length (LNG), environmental area (ENV-AREA), rectangle area (REC-AREA), locus length per second, locus length per environ area (L/E), and root mean square area. Romberg quotients (EC/EO) of these six parameters were also analyzed. The mean values of LNG, ENV-AREA and REC-AREA in the EC session in the migraine group were significantly greater than those in the controls (P < 0.05, Mann-Whitney rank sum test). Romberg quotients of all stabilometric parameters except the L/E in the migraine group were significantly greater than in the controls. Patients with episodic tension-type headache did not show any differences in the stabilometric study from the controls. The present findings suggest that patients with migraine show a significant increase of the body sway during the EC session, which indicates an underlying dysfunction in the vestibulospinal system.

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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro-apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild-type or mutant (A53T) alpha-synuclein and less likely with beta-synuclein in transfected COS-7 cells was found to induce Lewy body-like cytoplasmic inclusions. Unlike its full-length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin- and thioflavin S-positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild-type alpha-synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro-apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.