Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

ヒスイ デンカイエキチュウ ニ オケル リチウム キンゾク フキョク ノ ヒョウメン ハンノウ ニ カンスル ケンキュウ

京都大学0048新制・課程博士博士(工学)甲第9541号工博第2127号新制||工||1232(附属図書館)UT51-2002-G299京都大学大学院工学研究科物質エネルギー化学専攻(主査)教授 小久見 善八, 教授 垣内 隆, 教授 江口 浩一学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDA

Three-dimensional inversion of audio-magnetotelluric data acquired from the crater area of Mt. Tokachidake, Japan

Subvolcanic hydrothermal systems can lead to hydrothermal eruptions as well as unrest phenomena without an eruptive event. Historical eruptions and recent unrest events, including ground inflation, demagnetization, and a gradual decrease in the plume height, at Mt. Tokachidake, central Hokkaido, Japan, are related to such a subvolcanic hydrothermal system. This study investigates the three-dimensional (3-D) resistivity structure of Mt. Tokachidake to image its subvolcanic hydrothermal system. A 3-D inversion of the magnetotelluric data, acquired at 22 sites around the crater area, was performed while accounting for the topography. Our resistivity model was characterized by a high-resistivity layer at a shallow depth (50-100 m) and two conductors near the active crater and dormant crater. The high-resistivity layer was interpreted to be composed of dense lava, which acts as a caprock surrounding the conductor. The high conductivity beneath the active crater can be explained by the presence of hydrothermal fluid in fractured or leached zones within the low-permeability lava layer, as the sources of ground inflation and demagnetization were identified within the conductive zone immediately beneath the resistive layer. The resistivity structure was used to estimate the volume of hydrothermal fluid within the pore space. The minimum volume of hydrothermal fluid beneath the active crater that can explain the resistivity structure was estimated to be 3 x 10(6) m(3). This estimate is comparable to the water volume that was associated with the long runout and highly fluidized lahar in 1926. The resistivity structure and volume of hydrothermal fluid presented in this study can be used as a reference for further numerical simulations, which aim to reveal the mechanisms of recent unrest events and assess the risk of hazards, such as lahar