74 research outputs found

    Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models

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    パーキンソン病モデルへのペランパネルの有効性を確認 --パーキンソン病の進行抑制治療への期待--. 京都大学プレスリリース. 2021-04-05.[Background]: The intercellular transmission of pathogenic proteins plays a key role in the clinicopathological progression of neurodegenerative diseases. Previous studies have demonstrated that this uptake and release process is regulated by neuronal activity. [Objective]: The objective of this study was to examine the effect of perampanel, an antiepileptic drug, on α‐synuclein transmission in cultured cells and mouse models of Parkinson's disease.Methods: Mouse primary hippocampal neurons were transduced with α‐synuclein preformed fibrils to examine the effect of perampanel on the development of α‐synuclein pathology and its mechanisms of action. An α‐synuclein preformed fibril‐injected mouse model was used to validate the effect of oral administration of perampanel on the α‐synuclein pathology in vivo. [Results]: Perampanel inhibited the development of α‐synuclein pathology in mouse hippocampal neurons transduced with α‐synuclein preformed fibrils. Interestingly, perampanel blocked the neuronal uptake of α‐synuclein preformed fibrils by inhibiting macropinocytosis in a neuronal activity‐dependent manner. We confirmed that oral administration of perampanel ameliorated the development of α‐synuclein pathology in wild‐type mice inoculated with α‐synuclein preformed fibrils.[Conclusion]: Modulation of neuronal activity could be a promising therapeutic target for Parkinson's disease, and perampanel could be a novel disease‐modifying drug for Parkinson's disease

    Construction and response of a highly granular scintillator-based electromagnetic calorimeter

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    A highly granular electromagnetic calorimeter with scintillator strip readout is being developed for future linear collider experiments. A prototype of 21.5 푋0 depth and 180 × 180 mm2 transverse dimensions was constructed, consisting of 2160 individually read out 10 × 45 × 3 mm3 scintillator strips. This prototype was tested using electrons of 2–32 GeV at the Fermilab Test Beam Facility in 2009. Deviations from linear energy response were less than 1.1%, and the intrinsic energy resolution was determined to be (12.5±0.1(stat.)±0.4(syst.))%∕√퐸[GeV]⊕(1.2± 0.1(stat.)+0.6−0.7(syst.))%, where the uncertainties correspond to statistical and systematic sources, respectively

    Animal Model for Prodromal Parkinson’s Disease

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    Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, but various non-motor symptoms (NMS) often precede motor symptoms. Recently, NMS have attracted much attention as a clue for identifying patients in a prodromal stage of PD, which is an excellent point at which to administer disease-modifying therapies (DMTs). These prodromal symptoms include olfactory loss, constipation, and sleep disorders, especially rapid eye movement sleep behavior disorder (RBD), all of which are also important for elucidating the mechanisms of the initiation and progression of the disease. For the development of DMTs, an animal model that reproduces the prodromal stage of PD is also needed. There have been various mammalian models reported, including toxin-based, genetic, and alpha synuclein propagation models. In this article, we review the animal models that exhibit NMS as prodromal symptoms and also discuss an appropriate prodromal model and its importance for the development of DMT of PD

    Light-Driven Flying Balloons Based on Hybrids of Carbon Nanotubes and Cellulose Nanofibers

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    We have fabricated nanocarbon-based palm-sized cubic paper balloons that can be levitated by light irradiation. These paper balloons are composed of carbon nanotube (CNT) freestanding films and cellulose nanofiber (CNF) freestanding films. The number of CNT freestanding films (NCNT) and the number of CNF freestanding films (6-NCNT) among the six walls of the cube were varied. We investigated the effect of NCNT on the levitation behaviors under light irradiation. We found that the balloons were levitated when NCNT was greater than or equal to two. The levitation height was found to be increased by increasing NCNT
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