ゲンチョ ゼンソクジ ト ケンコウジ ノ シンタイナイ ブイ ノ ガイネン キノウ ノ リカイ オ チュウシン トシタ ケントウ

健康障害児の｢病気｣に関する教育の基礎資料を得るために､喘息児48名､健康児152名(小学校3年~6年)を｣対象に､身体内部位の機能に関する質問紙調査を実施した｡この結果は､2段階にわたり採点され､健康児の方が､身体内部位の機能に関する知識に関しては高得点をとり､その差も有意なものであった｡筆者の先行研究では､身体内部位､特に｢肺｣に関してのイメージは喘息児の方が健康児より早く出現するという傾向が報告されている｡この矛盾点を考察する中で､｢病気｣やそれに関する様々な情報の処理方法が異なることが示唆された｡つまり喘息児は､｢病気｣やそれに関わる情報について拡散的思考を用いて処理し､健康児は収束的思考を用いて処理しているように推測された｡過去､多くの研究は子どものパフォーマンスをもって｢病気｣や関連概念の研究を行ってきたが､この点については見直しが必要であろう

LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: Impairment of the kinase activity by Parkinson’s disease-associated mutations

AbstractLRRK2 is the causal molecule for autosomal-dominant familial Parkinson’s disease, although its true function, including its physiological substrates, remains unknown. Here, using in vitro kinase assay with recombinant proteins, we demonstrated for the first time that LRRK2 directly phosphorylates Akt1, a central molecule involved in signal transduction for cell survival and prevention of apoptosis. Ser473, one of two amino acids essential for Akt1 activation, was the target site for LRRK2. A knockdown experiment using intact cells also demonstrated LRRK2-mediated phosphorylation of Akt1 (Ser473), suggesting that Akt1 is a convincing candidate for the physiological substrate of LRRK2. The disease-associated mutations, R1441C, G2019S, and I2020T, exhibited reduced interaction with, and phosphorylation of, Akt1, suggesting one possible mechanism for the neurodegeneration caused by LRRK2 mutations.Structured summary of protein interactionsLRRK2phosphorylates Akt1 by protein kinase assay (View Interaction 1, 2, 3).LRRK2 phosphorylates MBP by protein kinase assay (View Interaction 1, 2).LRRK2 binds to Akt1 by pull down (View Interaction 1, 2, 3)

LRRK2 Phosphorylates Tubulin-Associated Tau but Not the Free Molecule: LRRK2-Mediated Regulation of the Tau-Tubulin Association and Neurite Outgrowth

Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi-functional domains, has been identified as the causal molecule for autosomal-dominant Parkinson's disease (PD). In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) LRRK2 phosphorylates tau at Thr181 as one of the target sites; and (iv) The PD-associated LRRK2 mutations, G2019S and I2020T, elevated the degree of tau-phosphorylation. These results provide direct proof that tau is a physiological substrate for LRRK2. Furthermore, we revealed that LRRK2-mediated phosphorylation of tau reduces its tubulin-binding ability. Our results suggest that LRRK2 plays an important role as a physiological regulator for phosphorylation-mediated dissociation of tau from microtubules, which is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport